A patient with persistent diarrhea was found to have biopsy-proved colitis with large numbers of the protozoan Blastocystis hominis present in stool. Extensive evaluation failed to reveal any other potential etiologic agent of acute colitis. Following treatment with a course of metronidazole, the patient became asymptomatic, B hominis was no longer present in stool, and results of a repeated biopsy were normal. These observations are consistent with the role of B hominis as a gastrointestinal pathogen.