Duke went down the first day, losing to nearly unknown Mercer.
Syracuse was bounced out on Saturday by Dayton a team that hadn't gone very far in 30 years.
Wichita State, one of the four regional No. 1 seeds and the only team that was undefeated this season, is undefeated no more. The Shockers were sent home Sunday by Kentucky.
Creighton, whose star Doug McDermott is arguably the best player in college basketball, is out after losing to lower-ranked Baylor.
As NPR's Tom Goldman said on Morning Edition, a "wide open tournament" is proving once again that madness really does descend in March when the Division I men's college basketball championship gets going. The upsets so far mean no one's going to win $1 billion from Warren Buffett and Quicken Loans, and that there are no perfect brackets among the millions that fans filled out for Yahoo Sports.
So with the "Sweet 16" now set, it's time for everyone to regroup. Maybe the team you picked to win it all is still in the tournament. Michigan State and defending champions Louisville, for instance, were popular picks before the tournament began and they're still playing. So are three of the regional No. 1 seeds: Florida, Arizona and Virginia. What's more, Kentucky was a preseason favorite of many fans to end up with the trophy, and the Wildcats seem to be playing some of their best basketball right now.
Give us your pick from among the 16 teams that are left. If you want to see the brackets so that you know the matchups for the next round of games, click here. Play resumes on Thursday.