High-titer anti-human immunodeficiency virus (HIV) antibodies reduced circulating HIV viral burden and has shown promise in previous small uncontrolled studies, warranting a larger controlled study of passive hyperimmune therapy (PHT) in persons with acquired immunodeficiency syndrome (AIDS). The objective of this study was to determine the efficacy and safety of PHT in 220 AIDS subjects in a 12-month double- blind placebo-controlled dosing study. Subjects were randomized to receive monthly infusions of 500 mL of plasma (full dose), 250 mL of plasma diluted in 250 mL of 5% human serum albumin (half dose), or 500 mL of 5% human serum albumin (placebo). Positive treatment effects occurred only in full-dose-treated subjects with baseline CD4 cell counts between 50 and 200 cells/mm3. Reduced mortality was observed, 1 death in 21 (full dose) versus 3 deaths in 21 (half dose) and 6 deaths in 30 (placebo) (P = .065). CD4 cells improved an average of 32.7 cells/mm3 over baseline (full dose) versus 0.9 cells/mm3 (half dose) and a loss of 3.5 cells/mm3 (placebo) (P = .043). No adverse effects or toxicity was noted in donors or recipients. Based on these findings, PHT appears to be a safe, promising therapy warranting further study.