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McFarlane will act as the executive producer on a reimagining of the cartoon, which follows the lives of two families of cavemen, the Flintstones and the Rubbles, and is set in the fictional prehistoric town of Bedrock.
Making references to The Simpsons and his own hit adult animated series Family Guy, MacFarlane joked: "I think America is finally ready for an animated sitcom about a fat stupid guy with a wife who's too good for him."
Seth has been a lifelong fan of The Flintstones - which was originally made by Hanna-Barbera and aired between 1960 and 1966 - and claims the first cartoon picture he ever drew aged two was of lead character Fred Flintstone.
Trademark humour
He has also promised not to change the format too much, though he is sure to add his own trademark brand of humour.
MacFarlane insists the characters will look the same as in the original series but he'll introduce new technology, like "what is the animal version of an iPad?"
The show will air on the Fox network in the US - which shows Seth's series' Family Guy, American Dad! and The Cleveland Show - and is due to go into production this year, with an on-air date set for 2013.
Kevin Reilly, President of Entertainment at Fox, added: "'The Flintstones are among the funniest and most beloved characters in television history, and we can't wait to introduce them to a whole new generation.
"Fox has long been home to iconic families like the Simpsons and [Family Guy's] the Griffins, so I have no doubt that the Flintstones and the Rubbles are going to fit right in on our air."
