Clostridium difficile colitis is a nosocomial infection that continues to cause significant hospital morbidity despite adequate treatment. This morbidity may be especially costly in the immunocompromised patient who now makes up a greater percentage of hospitalized patients. The purpose of this study was to evaluate if patients in immunocompromised states are at risk for relapse of Clostridium difficile colitis, and to determine the efficacy of metronidazole in these patients. A retrospective chart review was conducted of patients with Clostridium difficile colitis over a 1-year period between 1990 and 1991. From this study group, 114 patients were identified who had both positive Clostridium difficile toxin assays of fecal specimens and documented in-house clinical infection. There were 67 immunocompromised patients (59%) in the study group. Oral vancomycin was given alone in 41 (36%) patients, metronidazole was used in 36 (32%) patients, and a combination was given in 15 (13%) patients. Twenty-two (19%) patients received no antibiotic therapy and had their preceding antibiotics terminated. Twelve (10.5%) patients had documented relapses, and all had an immunocompromising condition. There was no statistically significant difference in relapse rates between the vancomycin and metronidazole-treated patients. We conclude that metronidazole, with its significantly lower cost, should be used as first-line therapy in immunocompromised patients.