Although liver test abnormalities are frequently identified in patients with acquired immunodeficiency syndrome (AIDS), the causes, evaluation, and outcome of jaundice in these patients have not been systematically evaluated. From August 1, 1990 through September 1, 1994, all human immunodeficiency virus (HIV)-infected patients with liver test abnormalities seen by the gastroenterology service at a large, inner-city hospital were prospectively identified. Jaundice was defined as a serum bilirubin concentration ≥3 mg/dL. The etiology of jaundice was determined by the pattern of liver biochemistry test abnormalities, radiographic studies, liver biopsy, clinical follow-up, and autopsy. During the study period, 541 HIV-infected patients (511 with AIDS) were evaluated for liver disease by our service; 36 of these patients had jaundice (7%). The most common causes of jaundice were drug- induced hepatitis, occurring in 11 patients (31%), and alcoholic liver disease, occurring in 5 (13%). Opportunistic infections or neoplasms were identified as the cause of jaundice in 11 patients (30%), with 4 having intrahepatic disease and 7 having extrahepatic disease. Multiple potential causes were seen in 3 patients. Abdominal ultrasonography (US) and computed tomography (CT) were helpful in suggesting the underlying cause of disease. The short-term mortality was high, with 9 patients dying during the hospitalization (25%) and 7 patients dying within 6 months of evaluation. Liver disease was the cause of death in 7 of these patients. In conclusion, jaundice is uncommon in AIDS and may result from a variety of both opportunistic and non-opportunistic etiologies. Drug-induced hepatitis is the most common cause and may be fatal. Long-term survival was poor.