We describe three patients with advanced human immunodeficiency virus (HIV) infection, two with colitis and one with cholestatic hepatitis, for whom results of detailed endoscopic and histologic studies were suggestive of invasive spirochetosis. In the two patients with colitis, colonoscopic evaluation revealed either diffuse ulcerations or pustules; in both cases, there was histologic evidence of extensive superficial cell necrosis and infiltration of the mucosa and lamina propria with acute inflammatory cells. Spirochetes in the mucosa and crypts were visualized by Warthin-Starry silver staining. Morphologically similar spirochetes throughout the liver specimen from the patient with cholestatic hepatitis were demonstrated by Warthin-Starry silver staining. Analysis with electron microscopy revealed these organisms to be loosely coiled spirochetes. Despite extensive evaluation, no other pathogens were identified. Invasive spirochetal infection, as defined by the results of Warthin-Starry silver staining of involved tissues, should be considered in the differential diagnosis of patients with HIV infection who have otherwise unexplained colitis or cholestatic hepatitis.