At least two people were confirmed dead. The Coast Guard said early Wednesday that crews were searching for two other people who were aboard the Learjet 35.
Shortly after taking off Tuesday night from a private terminal at Fort Lauderdale-Hollywood International Airport, the plane plunged into the water about a mile offshore.
A Federal Aviation Administration spokeswoman says the jet was carrying two pilots and two passengers to Cozumel, an island off Mexico's Yucatan Peninsula.
The National Transportation Safety Board is investigating.
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