Guard Richie Incognito knew LeSean McCoy's right knee was fine when the Bills running back was already gabbing in Buffalo's locker room during halftime.
"As long as Shady's talking, he's fine," Incognito said.
If knocking knees with 49ers linebacker Nick Bellore late in the first half couldn't slow down the player nicknamed, "Shady," what chance did the porous 49ers run defence have?
McCoy had 140 yards rushing and matched a career high by scoring three times as the Bills extended their winning streak to four with a 45-16 victory over San Francisco and its new starting quarterback Colin Kaepernick Sunday.
Outside the stadium, vendors sold shirts with Kaepernick's image in the sights of a rifle scope, and fans tackled a dummy dressed up like the quarterback. Nearby, other fans expressed support for the QB's protest movement.
The game against the Buffalo Bills marked Kaepernick's first start of the season, with Blaine Gabbert benched.
Kaepernick knelt on the 49ers' sideline, joined by linebacker Eli Harold and safety Eric Reid. To the left of the kneeling players, cornerback Rashard Robinson and safety Antoine Bethea stood for the anthem, each with an arm raised.
The entire Bills team stood on the sideline, as players and coaches have done all season.
Kaepernick was the only San Francisco player not wearing his helmet when the Niners took the field. He was loudly booed while jogging toward the sideline. He got off the 49ers' bus wearing a T-shirt with a picture of Muhammad Ali.
Outside New Era Field, one vendor was selling a T-shirt "Wanted: Notorious Disgrace to America," and with a picture of Kaepernick throwing a pass and a bullseye on his chest.
Another T-shirt featured a drawing of a kneeling Kaepernick with the words, "Shut Up and Stand Up!"
Kaepernick finished 13 of 29 for 187 yards, including a 53-yard touchdown pass to Torrey Smith. But San Francisco (1-5) couldn't finish drives, settling for three field goals by Phil Dawson, in losing its fifth consecutive game.
"I thought he was okay," coach Chip Kelly said of Kaepernick, whom he promoted over Blaine Gabbert following a 33-21 loss to Arizona. "But overall, offensively as a group, we need to run the ball better and we need to be better at the passing game."
Kelly wouldn't commit to who will start next week against Tampa Bay. "Yeah, we'll see," he said.
Meanwhile, Bills QB Tyrod Taylor threw two touchdown passes, helping Buffalo win four straight for the first time since the start of the 2008 season.
Buffalo's 312 rushing yards was the franchise's best since 1992, and the Bills blew the game open by scoring 21 points over a span of 7:02 straddling the third and fourth quarters.
Taylor completed a 30-yard pass to Justin Hunter. Then the 49ers were stopped for no gain on a fourth-and-one at Buffalo's 40.
After McCoy put the Bills up 31-16 with 10:53 left in the fourth quarter, the Bills got the ball back after Keshawn Martin fumbled the kickoff. Two plays later, Taylor hit Robert Woods for a five-yard touchdown pass.
McCoy scored twice on 18-yard runs and another on a four-yard scamper in his second meeting against Kelly. McCoy expressed bitter feelings toward Kelly for trading him from Philadelphia to Buffalo.
"To sit here and tell you that it didn't affect me last year, I would be lying," McCoy said. "But I'm past that. It's a whole year later."
McCoy's three-TD game was the third of his career, and first since Philadelphia's 45-19 win over the Rex Ryan-coached Jets in 2011. He became Buffalo's first player to score three times rushing since Willis McGahee had four TDs against Seattle in 2004.
Backup Mike Gillislee closed out the scoring with a 44-yard run. Buffalo's 45 points were the most since a 49-31 win at Cincinnati in 2010.
With three sacks on Sunday, Buffalo increased its total to 20 – one fewer than the team had all last season.