The crash took place about 6:35 a.m. local time on SR 40 in Marion County, the Florida Department of Highway Safety and Motor Vehicles said.
Eight people died at the scene and 45 injured were taken to medical facilities, including eight in critical condition, James Lucas with Marion County Fire Rescue said.
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The crash involved a bus transporting over 50 migrant farm workers and a Ford Ranger truck.
The two vehicles sideswiped each other.
The Florida Highway Patrol said the bus was traveling west, and the pickup truck traveling east crossed the center line.
The bus left the road, crashed through a fence and hit a tree before rolling over.
The truck driver was also seriously injured.
The workers were being transported to Cannon Farms in Dunellon, which has been harvesting watermelons.
"We will be closed today out of respect to the losses and injuries endured early this morning in the accident that took place to the Olvera Trucking Harvesting Corp.," Cannon Farms announced on its Facebook page. "Please pray with us for the families and the loved ones involved in this tragic accident. We appreciate your understanding at this difficult time."
Cannon Farms describes itself as a family owned commercial farming operation that has farmed its land for more than 100 years, focusing now on peanuts and watermelons, which it sends to grocery stores across the U.S. and Canada.
West Highway 40 is closed in the area, and will be for most of the day, officials said. A detour is in place.
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Florida Highway Patrol is on the scene investigating.
Marion County is about 30 miles south of Gainesville, Florida.
CNN, the Associated Press and ABC News contributed to this report.