JACKSONVILLE, Fla. – There was nothing Peyton Manning could do to prevent this outcome – unless he decided to play defense or special teams.

Rookie Maurice Drew ran for a career-high 166 yards and two touchdowns, had a 93-yard kickoff return for a score, and the Jaguars literally ran the Colts out of town and maybe out of contention for home-field advantage in the AFC with a surprising 44-17 victory Sunday.

Drew ran so much he started cramping up in the third quarter and had to get intravenous fluids.

Fred Taylor was equally effective against the league’s worst run defense, gaining 131 yards on nine carries before leaving the game with a sore right hamstring.

By then, the Jaguars (8-5) were ahead 34-10 and coasting to their first win against Indianapolis since 2004. The Colts (10-3) had won three in a row in the series and were looking to clinch their fourth consecutive division title.

Now, they’re trying to regroup from a third loss in four games and wondering whether they’ve gone from the leading candidate to secure the conference’s No. 1 seed to a possible wild-card team.

Indianapolis – which finishes the season against Cincinnati, Houston and Miami – knows what went wrong. The defense hasn’t been able to stop the run all season.

The Colts allowed a franchise record 375 yards rushing Sunday. They gave up 251 yards on the ground in the first half – nearly 100 yards more than they averaged giving up in the previous 12 games.

Taylor set the tone with a 76-yard run on Jacksonville’s opening play. Drew scored on the next play. It was the start of a team rushing record for the Jaguars, breaking the previous mark of 244 yards rushing set in December 2000 against Cleveland.

Indianapolis’ defensive woes overshadowed Marvin Harrison’s accomplishment. Harrison became the fourth player in NFL history with 1,000 receptions Sunday, joining Jerry Rice, Tim Brown and Cris Carter.

Harrison finished with six catches for 101 yards. Reggie Wayne had eight receptions for 110 yards.

Manning and Harrison hooked up for a 42-yard gain on the game’s opening play. It could have been a touchdown, but Manning badly underthrew Harrison. Three plays later, Brandon Stokley dropped a perfect pass in the end zone on third down – a momentum-changing play.

The Jaguars responded with Taylor’s long gain and Drew’s first TD run.

Jacksonville ran at will, controlled the clock and could have had a much bigger lead. But Josh Scobee missed a field goal, David Garrard threw an interception in the end zone and the Jags failed to convert a fourth-down play in Colts territory.

The Jaguars made up for their mistakes with a blocked punt, an interception and constant harassment of Manning – giving coach Jack Del Rio a second win in as many games while wearing a sports coat and tie on the sideline.

Del Rio’s defense finished with two sacks and forced Manning into nine consecutive incompletions at one point. Manning finished 25-of-50 for 313 yards.

Manning had done so much this season to help the Colts overcome their defensive woes, leading clutch drives or putting together big games to help his team win close games against the Giants, Jaguars, Jets, Tennessee, Denver, New England and Buffalo.

AP-ES-12-10-06 1613EST