The storms tore across Arkansas, Tennessee, Kentucky, Mississippi and Alabama, overturning trucks, trapping people, ripping up houses, smashing cars and uprooting trees.
By this morning, tornado watches were in effect for the Florida Panhandle, western Georgia and eastern Tennessee.
"Based on reports from our local offices, the death toll now stands at 45. That is 26 in Tennessee, 13 in Arkansas, one in Alabama and five in Kentucky," said Roger Erickson, a meteorologist with the National Weather Service in Fort Worth.
Tennessee was the hardest hit state. Emergency officials said 149 people were injured in their state alone.
A tornado struck the Columbia Gulf Transmission company in Hartsville, Tennessee, and set off a natural gas fire that lit up the early morning sky, officials said.
The twister flattened the nearby home of one resident.
"It just took the house and everything and my horses and my dog," Dara Reasonover told CNN. "I don't know if they're alive or dead, but we'll make it."
Tennessee and Arkansas were among the 24 "Super Tuesday" states that held nominating contests before November's presidential election.
Several candidates expressed condolences to victims as they addressed supporters.
Earlier today, Kentucky emergency officials put the death toll in their state at seven.
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