A freeway bridge over the Mississippi river has collapsed during the evening rush hour, sending cars into the water.
An entire span of the four-lane I-35W bridge in the city of Minneapolis fell into the river at 1805 (2305GMT).
Local officials said three people had died. Some people were stranded on parts of the bridge still standing.
The US Department of Homeland Security said there was no reason to suspect the fall of the bridge, which had been undergoing repairs, was terror-related.
Traffic had been moving slowly at the time of the incident as only one lane was open in either direction because of the construction work on the arched bridge, which was built in 1967.
Vehicles were reported to have fallen into the river, and a large plume of smoke was seen billowing into the sky from a lorry.
It was feared that a school bus had fallen into the river, but it is now known to have stopped on the edge of a collapsed section, and 30 children have been taken to safety with minor injuries.
Tons of concrete crashed 64 feet (20 metres) into the water after the interstate bridge crumbled.
Television news pictures showed boats searching for injured people and cars stranded on large chunks of concrete in the water.
Eyewitnesses said they heard a rumbling sound as the 40-year-old structure collapsed into the river.
Leone Carstens, a local resident, told the Minneapolis Star Tribune newspaper: "First I heard this huge roar.
"I was at my computer. Initially I thought: 'Wow was that an airplane?'"
Eyewitnesses said they saw people in the water and rescuers carrying survivors up the riverbank.
A nursing supervisor at Hennepin County Medical Center told local WCCO radio: "We have multiple patients. Some critical, some non-critical."
Chris O'Connell, a Minneapolis reporter, told the BBC: "It is a very chaotic scene here. To call this a catastrophe would be an understatement.
"We're still trying to get a count on how many, but a lot of people went into the river."
Russ Knocke, a spokesman for the Department of Homeland Security, told the AFP news agency: "There are no indications of a nexus to terrorism at this time."