Manhattan hung with defending national champion Louisville for 38-plus minutes, giving the Cardinals all they could handle.

The 13th-seeded Jaspers looked entirely capable of pulling off the biggest upset on the first full day of the NCAA tournament. Until Louisville's two most reliable players — seniors Russ Smith and Luke Hancock — took over.

Smith and Hancock delivered dagger after dagger, knockout blows that sent Manhattan home with a 71-64 loss Thursday night in the Midwest Region.

"That's what happens when you play great teams," Manhattan coach Steve Masiello said. "You give them that one opportunity, they make you pay. That's why this team is a defending national champion and top five in the country."

Smith finished with 18 points, including 11 from the free-throw line, and Hancock added 16. But it was what they did in the final few minutes that will stick with the Jaspers (25-8) for a while.

Manhattan led 58-55 with less than 4 minutes remaining — outplaying Louisville for most of the second half — before the Cardinals came alive from behind the arc.

Smith got things going with a game-tying 3 from the wing. Hancock's shots were even bigger. He stole an inbound pass, got fouled and made both free throws. He hit the first of two 3s with a little more than a minute left and then sank a wide-open look from behind the arc with 28 second remaining.

Those shots propelled fourth-seeded Louisville (30-5) into the round of 32, where it will face fifth-seeded Saint Louis on Saturday in the Midwest Region.

"We needed a couple bounces to go our way," Hancock said. "Nobody wants to go home on the first day. We're trying to build a legacy. This is a first step."

Manhattan will try to build off the gut-wrenching loss.

"This loss definitely hurts," said George Beamon, who came in as the Jaspers' leading scorer but finished with seven points. "At least we lost to a great Louisville team. ... Those guys brought it, but it definitely hurts. Definitely don't want to feel this ever again, and we want to get our younger guys ready so they won't have to feel like this again."

Louisville coach Rick Pitino wanted nothing to do with Manhattan, which is coached by his former assistant, Masiello. And now everyone knows why.

Masiello served as Pitino's ball boy with the NBA's New York Knicks in the 1980s, played for him at Kentucky (1996-1997) and then spent another six years coaching alongside him at Louisville (2005-11). They know each other inside and out, with Masiello molding Manhattan to mirror the Cardinals.

It showed.

The Jaspers attacked Louisville's weaknesses and gave the Cards fits on the defensive end.

"That's one of the best coaching jobs that I have seen in my 39 years," Pitino said. "He just made us have to guard on the perimeter with four guards. ... That's why I didn't want to play them, because I'm sick inside losing to one of my players."

Masiello was equally disappointed in the draw and the outcome.

"It's emotional. It's emotional," he said. "You look down, and the guy who kind of made you who you are is your enemy for 40 minutes. So it's tough. You know, it's an honor to be on the other sideline, but it's about the kids. It's not about me. My kids played. Their kids played. I think it was two very good basketball teams.

"But it's tough. It hurts. You know, if I'm going to lose to anyone, I guess lose to him."

The lead changed hands a few times in the second half, but when Manhattan went ahead 58-55 on Rhamel Brown's layup, it looked like Louisville would go down. But Smith and Hancock helped their team stave off elimination.

"We could have folded and we didn't," Pitino said. "I think we'll take a big step forward from here."

Harrell finished with 12 points and 13 rebounds for the Cards. Chris Jones chipped in 11 points.

Ashton Pankey led Manhattan with 16 points. Emmy Andujar added 13 points, and Michael Alvarado chipped in 10.

"Unfortunately, there's only one team that gets to celebrate this time of year, and you know, I thought we came out, I thought we executed some things well," Masiello said. "I thought Louisville bothered us. But I'm proud. I'm proud of my guys. I'm proud to coach these men."