By DAVE GOLDBERG
AP Football Writer
INDIANAPOLIS -- Peyton Manning is adjusting to being without Marvin Harrison. Tony Dungy is finally adjusting to instant replay.
So the Indianapolis Colts are on the verge of their fifth straight AFC South title.
Manning, hampered by a lack of receivers for the past six weeks, threw four touchdown passes, two after the Colts won replay challenges, to beat Jacksonville 28-25 Sunday and take a two-game lead with four games to go.
It was the second victory by the Colts (10-2) over Jacksonville (8-4) this season, essentially giving them a three-game lead with four games left in a division they've controlled since Tennessee won it the first year of the current configuration.
"I feel great about where we are right now," said Dungy, who during the early years of the challenge system couldn't win any, let alone two, as he did in a bizarre first quarter Sunday that included three challenges.
"Going into the fourth quarter of the season, we've got a good lead in the division and we're second in the conference. If we'd lost, we'd have felt we'd have to win all four of our last games."
Jacksonville's Jack Del Rio all but conceded the title.
"In all likelihood, they'll win the division," said Del Rio, whose team still leads the AFC wild-card race. "They still have to play it out, but they deserve it. We didn't quite get it done today, but I saw a lot of good things."
Having lost to unbeaten New England, the Colts have almost no chance to get home-field advantage for the AFC playoffs. To get a first-round bye, they have to finish second in the conference and went into Sunday a game ahead of Pittsburgh for that spot.
The Colts' first two TDs came after challenges.
The first one came on the Jaguars' opening possession when Robert Mathis sacked David Garrard and knocked the ball free. Officials first ruled Jacksonville recovered at its 11, but Dungy appealed and referee Terry McAuley ruled the Colts' Raheem Brock recovered.
"I never thought there was a question," Dungy said. "I saw Raheem get the ball. He was down. Then someone knocked into him and knocked it loose."
Two plays later, Manning threw a 5-yard TD pass to Dallas Clark.
On the Colts' next possession, officials ruled Ben Utecht fumbled. Dungy appealed, McAuley ruled it an incomplete pass, and on the next play, Manning threw a 48-yard TD pass to Reggie Wayne, who finished with 8 catches for 158 yards.
Manning, who was 19-of-28 for 288 yards, also threw a 14-yarder to Clark and a 1-yard shovel pass to running back Luke Lawton for scores. He now has 23 TD passes for the season, tying him with Dan Marino as the only quarterbacks to throw more than 20 in each of their first 10 NFL seasons.
It was his first game with four touchdown passes since last December 18 against Cincinnati. He has been hampered in recent weeks by the loss of Harrison, who has missed seven of the last eight games with a knee injury allowing teams to concentrate on Wayne. The Colts had only three wide receivers active for Sunday's game.
"It's been tough getting used to new people and for the new people to get used to me," Manning said. "I thought we finally got some things going today."
Jacksonville, which ran for 168 yards, finally got going after the second Manning TD pass. The Jags took more than 11 minutes to go 84 yards in 16 plays to cut it to 14-7 on Maurice Jones-Drew's 2-yard run.
However, Manning drove the Colts right back downfield, hitting Clark from 14 yards out to make it 21-7 at intermission. Capping another time-consuming drive to start the second half, the Jaguars cut it to 21-14 on Garrard's 2-yard pass to Marcedes Lewis.
"To come out in the third quarter and put a stamp on it: 'We're not going anywhere. We're going to be here for 60 minutes,' " Garrard said.
Reggie Nelson's end-zone interception of Manning ended an Indy threat and Josh Scobee's 47-yard field goal cut the Colts lead to 21-17 early in the fourth quarter. But the Colts scored again on the shovel pass to Lawton, who was just signed this week after being cut earlier in the season.
"It was great on Luke's part that he knew the play," Manning said. "We just brought him back this week. It's kind of a funny TD pass for me but I'll take it."
Antoine Bethea's interception of Garrard, the first against the Jacksonville QB in 231 passes this season, stopped one drive. But he threw a 17-yard TD pass to Dennis Northcutt, then bulled in for a 2-point conversion, cutting it to 28-25 with 2:47 left.
Indianapolis ran out the clock to win it.
Garrard was 24-of-29 for 257 yards for Jacksonville. Fred Taylor had 104 yards in 14 carries, his second straight 100-yard game after having none previously this season.
Notes: Brock left the game in the first half and didn't return. His injury wasn't disclosed. ... Jacksonville defensive end Reggie Hayward injured a groin muscle. Del Rio said he didn't know Hayward's status. ... Wide receiver Anthony Gonzalez scored what appeared to be his first career touchdown for the Colts, but it was called back for offensive interference. "I didn't see that he did anything," said Manning, who noted his first career TD pass was taken away on the same penalty.