Police said the pilot, his wife and a friend of the couple were killed in the crash, which occurred late Sunday shortly after takeoff from Orlando Executive Airport.
The guest house, which was on a larger property, was empty at the time of the crash.
Police said residents of the property were in the main house, but they escaped injury.
The cause of the crash was not immediately known. The Federal Aviation Administration and the National Transportation Safety Board have opened an investigation.
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