A 2.5-year-old captive female mandrill (Papio sphinx) died following a protracted course of intermittent abdominal bloat, diarrhea, and severe weight loss. Necropsy revealed emaciation and marked gastrointestinal distention with gas and ingesta. Histologic evaluation revealed severe diffuse granulomatous enterocolitis and mesenteric lymphadenitis with massive numbers of 1-2-microm acid-fast bacilli within macrophages. Additionally, there was moderate to severe multifocal myocardial and vascular amyloidosis, moderate multifocal pyogranulomatous interstitial pneumonia with no acid-fast bacteria, and moderate multifocal glossal candidiasis. Samples of feces, ileum, and colon were positive for Mycobacterium avium subsp. paratuberculosis by radiometric culture and a polymerase chain reaction-amplified DNA probe specific for the insertion sequence IS900 of this organism.