A 40-year-old bisexual man with the acquired immunodeficiency syndrome developed abdominal pain and bloody diarrhea. At sigmoidoscopy, the mucosa of the rectum and sigmoid colon was edematous, erythematous, and friable, with multiple linear and oval erosions. Histologic examination of rectal biopsies demonstrated innumerable acid-fast bacilli free and within macrophages of the lamina propria. Mycobacterium avium-intracellulare was cultured from the rectal biopsy specimens. Pulmonary tissue and bone marrow cultures also demonstrated this organism. Therapy with several antimycobacterial agents resulted in improvement of symptoms. Among immunocompromised patients the spectrum of enteric pathogens causing colitis should be expanded to include Mycobacterium avium-intracellulare, a potentially treatable organism.