Both diarrhea and colitis associated with clozapine have been reported. In this article, the authors present a case of clozapine-induced microscopic colitis (MC)-the first reported in the literature. The definitive diagnosis was suggested on colon biopsy, which showed an intraepithelial lymphocytosis (with >20 lymphocytes for every 100 epithelial cells) more striking in the surface epithelium than in the crypts. In addition, there were a mixed inflammatory infiltrate in the lamina propria (with lymphocytes predominating over eosinophils and neutrophils), an architecturally preserved colonic mucosa (particularly in the crypts), and a subepithelial collagen band normally thickened (<10 microm). Clozapine was thought to be the culprit and discontinued. After some days, the patient gradually improved. Diarrhea and spiking fever disappeared within 72 hours. Multiple colon biopsies taken after 7 days from the discontinuation of the clozapine revealed no abnormal histological findings. It is important to clarify the issue of clozapine-induced MC because MC may require the use of expensive or potentially toxic treatments and can occasionally be life-threatening (eg, hypokalemia). Thus, any case of MC that can be cured by withdrawal of the clozapine must be investigated and identified.