To evaluate the incidence, characteristics, and risk factors of adverse drug reactions (ADRs) in patients with human immunodeficiency virus (HIV) disease, we conducted was a prospective observational study of inpatients with HIV disease. The study was conducted in a public teaching hospital affiliated with the University of California, San Francisco. We reviewed daily the hospital records of all eligible inpatients throughout their hospitalization for potential ADRs. Potential ADRs were independently evaluated by two of the authors with regard to the extent of their causal association(s) with implicated drug(s) using a previously validated algorithm. Type (A, augmented; B, bizarre) and severity (mild, moderate, severe) were also evaluated. Among 495 patient admissions involving 390 eligible patients, 173 potential ADRs were identified, of which 118 (68.2%) had a probable or definite causal relationship to the implicated drugs. These probable or definite ADRs occurred among 79 (20%) eligible patients; 82 ADRs (69.5%) were classified as augmented (type A) and 36 (30.5%) were classified as bizarre (type B) reactions. Skin rash was the most frequent (17%) ADR encountered. Of the medications causing ADRs, 70% were antimicrobial drugs. Significant independent risk factors for developing ADRs included advanced stage of HIV disease, intake of a greater number of medications, and longer hospital stay. A high percentage of patients with HIV disease developed ADRs. Skin rash was the single most common kind of ADR. Advanced stage of illness and prolonged drug exposure were the only risk factors for ADRs.