Cefoxitin-treated hamsters were first colonized with a nontoxigenic strain of Clostridium difficile, and then a toxigenic strain of C. difficile was administered. Toxigenic C. difficile was suppressed to a mean cecal population level of less than 0.2% of that found in control animals given only toxigenic C. difficile after cefoxitin treatment. Colonization with nontoxigenic C. difficile before toxigenic C. difficile was associated with 93% survival, as opposed to 21% survival of the control animals. Simultaneous administration of nontoxigenic and toxigenic C. difficile did not lead to suppression of toxigenic C. difficile and conferred no protection. These results are in keeping with previously established concepts of bacterial interactions on body surfaces and may have therapeutic implications.