Democrat Travis Childers won a comfortable victory, 54 percent to 46 percent, over his Republican opponent for an open House seat in Mississippi on Tuesday night. After Childers' victory, even normally confident House Republican leaders acknowledged the obvious: The loss of a third long-time Republican district in the past two months is a devastating setback for the GOP, and it appears to place Democrats in the driver’s seat for House elections in November.

“The results in Miss.-01 should serve as a wake-up call to Republican candidates nationwide,” said House Minority Leader John Boehner, R-Ohio. “As I’ve said before, this is a change election, and if we want Americans to vote for us, we have to convince them that we can fix Washington.” In a clear swipe at President Bush (whom he did not mention by name), Boehner added, “Our presidential nominee, Sen. [John] McCain, is an agent of change; candidates who hope to succeed must show that they’re willing and able to join McCain in leading [a] movement for reform.”

National Republican Congressional Committee chairman Tom Cole was equally blunt about his party's prospects. “Tonight’s election highlights two significant challenges Republicans must overcome this November," he said. "First, Republicans must be prepared to campaign against Democrat challengers who are running as conservatives, even as they try to join a liberal Democrat majority.”

Cole then added, “The political environment is such that voters remain pessimistic about the direction of the country and the Republican Party in general. Therefore, Republicans must undertake bold efforts to define a forward-looking agenda that offers the kind of positive change voters are looking for.”

Although House Republicans plan to unveil an “American families agenda” on the East Front steps of the Capitol this afternoon, such an effort may be too little, too late.

House Democrats, for their part, pointed to the Mississippi outcome as a measure of their success. House Speaker Nancy Pelosi, D-Calif., said Childers' "message of positive change and bipartisan progress" proved "that Americans across our country want real solutions and reject Republicans' misleading and negative attacks.”

The often-caustic Democratic Caucus chairman Rahm Emanuel, D-Ill., summarized the outcome: “Change 3, Status Quo 0.” He added, “The American people are rejecting Bush Rubberstamp Republicans and casting their votes for real change.”

Republican attempts to link their opponents to Pelosi and likely Democratic presidential nominee Barack Obama have not only failed but may have actually backfired. Some GOP strategists had held out hope that their fate would improve when they forced local Democrats to run on the ballot with their national ticket.

Tuesday’s outcome was stunning for both its clear margin of victory and the impressively large voter turnout -- a sign of national Democratic enthusiasm. Childers took 20 of the 24 counties in the northern Mississippi district; more than 106,000 votes were cast, compared with 67,000 ballots in the first round of voting on April 22.

The story is the same in Mississippi as it was in Democrats' other special-election victories in Illinois and Louisiana this spring. But unlike those two other contests, in which the GOP cited flaws in its local candidates, nervous Capitol Hill Republicans recently admitted they would have no excuses for losing the Mississippi district, where Bush won 62 percent of the vote in 2004. Vice President Dick Cheney even made a last-minute appearance for Davis on the eve of the election in an attempt to rally the faithful. “Tough night for sure,” a House GOP leadership aide e-mailed about the outcome.

Mississippi GOP nominee Greg Davis, who was defeated Tuesday, served as a state representative and local mayor for 18 years, and he embraced conventional GOP dogma. In an interview with a local newspaper, he pledged to “lead the fight to end illegal immigration, put an end to wasteful government spending and fight for the God-given rights of the unborn.”

As late as Tuesday afternoon, House Democrats were less than confident about the outcome. In a preview of the election, Democratic Congressional Campaign Committee communications director Jennifer Crider cautioned, “Win or lose, there is no good news in today’s election for House Republicans.” She cited the GOP’s big spending on the contest, “the damage to the Republican brand and the depth of the NRCC’s problems this cycle.”

The historical significance of the House Democrats’ success is hard to deny. As noted by DCCC chairman Chris Van Hollen, this was the first time in more than 30 years that Democrats “picked up three Republican seats in special elections in one cycle.” As a result, he added, “There is no district that is safe for Republican candidates because President Bush’s failed policies have hurt every community in America.”

With Democrats increasing their House control to 236 to 199, the three special-election wins virtually shut the door on Republican attempts to regain House control in November. Senate Republicans' challenge will be to limit the loss of additional GOP seats -- especially with the retirement of 25 more Republicans in the House and five in the Senate, according to CongressDaily (subscription). By contrast, only seven House Democrats are not seeking reelection, and no Democratic senators are retiring this fall.

The special-election losses have been all the more galling for Republicans because they resulted from unusual midterm resignations that were not caused by the normal factors, such as illness, legal problems or a move to another government post. This House seat, for example, was vacated when GOP Rep. Roger Wicker was appointed to fill the Senate opening caused by the December resignation of veteran Republican Sen. Trent Lott. (R). Lott and Rep. Richard Baker of Louisiana both took lucrative Washington lobbying and trade-association jobs, and former House Speaker Dennis Hastert returned home to Illinois.

After a 12-year span ending in January 2007 during which Republicans dominated the House and held the Senate majority for all but 19 months, the era of GOP control suddenly seems unlikely to return anytime soon.