Staying unbeaten through October would be impressive by nearly any other NFL team's standards, but to Peyton Manning and the Indianapolis Colts, it's practically evolved into an annual expectation.

As they try to move to 7-0 for the fourth time in five years, the Colts can extend their franchise-record regular-season winning streak to 16 on Sunday when they begin a three-game homestand against the San Francisco 49ers.

Indianapolis (6-0) was hardly convincing in its first two victories, beating Jacksonville by two points at home and surviving to win 27-23 at Miami despite having possession for fewer than 15 minutes.

The Colts, however, have been dominant in winning their last four games, albeit against opponents with a combined 6-19 record. They've won by an average of 24.0 points, and came out of their bye week to throttle St. Louis 42-6 last Sunday in the most lopsided victory of Manning's 12-year NFL career.

"Coming off a bye week, you never know how guys are going to respond or react," tight end Dallas Clark told the Colts' official Web site. "We came out with a purpose, and that shows you the leadership on this team. ... We have a lot of guys who have been around the block a few times."

No rookie coach since the 1970 merger has won his first seven games, but Indianapolis' Jim Caldwell has a chance to do that Sunday along with Denver's Josh McDaniels.

The Broncos and New Orleans are also 6-0, but an undefeated start to the season is hardly new to Indianapolis. Including the Saints and Broncos, there have been nine teams since 2005 to begin a season with at least six straight victories. Four of those unblemished records have belonged to the Colts, who have extended their record to at least 7-0 on each previous occasion.

Manning has again been the catalyst, averaging 313.3 yards passing, throwing for 15 touchdowns and leading the league with a 114.5 passer rating. He's had no Marvin Harrison for the first time in his career, No. 2 receiver Anthony Gonzalez has been out since injuring his knee in Week 1 and top target Reggie Wayne suffered a groin injury against the Rams.

While Wayne's groin issue doesn't appear to be serious, rookie running back Donald Brown hurt his shoulder last Sunday and could sit out this game. Gonzalez appears to be at least a week away from playing.

Though Manning has played at an All-Pro level, Indianapolis' defense has been impressive as well. The Colts are second in scoring defense (12.8 points per game) and ninth overall (291.7 yards per game). They haven't allowed a touchdown in eight quarters even while missing injured cornerback Marlin Jackson, who isn't expected to play Sunday, but safety Bob Sanders - the 2007 defensive player of the year - returned last week after missing the first five games following knee surgery.

"It's been a lot of fun," safety Antoine Bethea said. "Everybody is making plays, from the defensive line to the linebackers to the defensive backs. It's great when you can go out and have a good time and not have a lot of stress."

The Colts are beginning their first three-game homestand since 1999 against San Francisco (3-3), which has the NFL's 29th-ranked offense (272.0 ypg) but is armed with a new starting quarterback.

Former No. 1 overall draft pick Alex Smith, largely deemed a bust after three ineffective seasons and a 2008 lost due to a shoulder injury, relieved Shaun Hill after halftime Sunday in Houston with San Francisco in a 21-0 hole.

Smith couldn't complete the comeback but looked sharp, completing 15 of 22 passes for 206 yards and three touchdowns before a late interception sealed the 49ers' 24-21 loss.

On Monday, coach Mike Singletary announced Smith will start over Hill in Indianapolis.

"I don't know if I'd say surprised. I don't know if I was anticipating it, either," Smith said. "It's the opportunity I've been waiting for - (I'm) happy."

All three of Smith's touchdowns went to tight end Vernon Davis, but he also completed three passes to rookie Michael Crabtree, who was making his NFL debut after ending his lengthy holdout. Crabtree finished with five receptions for 56 yards.

"All of the hard work that he did while he wasn't here, it showed," Singletary said. "All of the studying that he did while he wasn't here, it showed. So it was good to see."

Tailback Frank Gore returned after missing three games with an ankle injury but was held to 32 yards on 13 carries, and it might not get any easier against the Colts. Right tackle Tony Pashos broke his left shoulder blade against Houston, ending his season in the first game he was replacing Adam Snyder.

Manning is 1-2 in his career against San Francisco, throwing six interceptions. Two of those came in the last meeting but the Colts won 28-3 on Oct. 9, 2005, as Smith went 9 of 23 for 74 yards and four interceptions in his first NFL start.