The program marked its 200th episode with an episode that included animated appearances of several religious leaders, including Buddha who was shown using drugs.
But it was showing Mohammed as a human wearing a bear suit that caught the attention of operators of a Web site maintained by Revolution Muslim. Any physical representation of Mohammed is considered blasphemous by Muslims.
Revolution Muslim warned that "South Park" creators Matt Stone and Trey Parker would "probably end up like Theo Van Gogh" for doing "stupid" things.
Van Gogh was killed in 2004 by a militant Muslim in reaction to a movie Van Gogh made about Muslim women.
Revolution Muslim listed addresses for Comedy Central, the "South Park" production office and a house owned by Parker and Stone.
It is far from the first time "South Park" has drawn controversy. A staple of the early days of the program, which debuted in 1997, was the death of the character Kenny in each episode. Also, Isaac Hayes quit in 2006 as the voice for the character Chef, saying he didn't like the way the program depicted Scientology.