Clostridium difficile has been implicated in the relapse of ulcerative colitis. Controversy exists over this role and its relationship to sulphasalazine exposure. Sixty two of 77 patients with a documented relapse of ulcerative colitis were investigated for the presence of Clostridium difficile, or its toxin, prior to hospitalization. There was a low incidence of detection which was related to antibiotic exposure (2/62). Sampling during the treatment period showed that the occurrence of Clostridium difficile in the stool was related to antibiotic treatment (2/66). Fifty six percent of patients were taking sulphasalazine, none of whom became culture or toxin positive. This study demonstrates that Clostridium difficile is not related to relapse of ulcerative colitis and is not secondarily acquired during relapse unless the patient is exposed to antibiotics. Sulphasalazine does not predispose to acquisition of Clostridium difficile. There is no role for routine screening or treatment of Clostridium difficile in ulcerative colitis.