The Florida Highway Patrol said the smashes involving 12 cars and six or seven trucks occurred shortly before 4 a.m. on Interstate 75 after smoke from a marsh fire combined with fog to reduce visibility on both the northbound and southbound lanes.
Eighteen people were transported to Shands Hospital emergency room, six of them to a trauma center for people in critical condition, according to hospital spokeswoman Alison Wilson.
Eight of the people treated in the emergency room had been released from the hospital by mid-afternoon.
"It's tragic. It's probably the worst one (accident) I've seen in 27 years," Florida Highway Patrol spokesman Patrick Riordan told Reuters.
Riordan said investigators are still trying to determine how many separate collisions occurred on the interstate, which is a main artery through Florida.
In one crash, two cars and a tractor trailer caught fire and melted asphalt on the road, Riordan said. The interstate remained closed hours later while the investigation continued, and an analysis of the road pavement was under way to determine whether it could be safely re-opened, he said.
Riordan said he had no information yet on the ages or gender of the victims. He said several people died in one car. Crumpled cars littered northbound and southbound lanes and in the grass shoulders of the interstate.
Gainesville is home to Florida's flagship university, the University of Florida. The marsh fire was in or near Paynes Prairie Preserve State Park south of town.
Florida Forest Service investigators are trying to determine whether the fire was set intentionally, Ludie Bond, a spokeswoman for the service, told Reuters. A lack of rain in recent months meant the fire spread quickly through the parched prairie.
(Reporting By Barbara Liston; Editing by Corrie MacLaggan adn Tim Gaynor)