Visceral protothecosis mimicking sclerosing cholangitis in an immunocompetent host: successful antifungal therapy. A healthy 39-year-old man who had clinical findings consistent with sclerosing cholangitis was found to have systemic protothecosis at surgery. Severe granulomatous inflammation and palpable nodules were found in the gallbladder, on the surface of the liver, and in the duodenum. Prototheca wickerhamii was detected in biopsied specimens and stool; the titer of indirect fluorescent antibody to this organism was 1:2,000. The patient recovered after a short course of treatment with amphotericin B and 3 months of oral therapy with ketoconazole. He had no other concurrent illness and had no abnormality in his immune system. This is the second reported human case of systemic protothecosis. An elevated IgG level, an elevated erythrocyte sedimentation rate, eosinophilia, and abnormal levels of enzymes in the liver were found in both cases. Protothecosis should be considered in the differential diagnosis of hepatic and biliary inflammatory diseases of uncertain etiology. 