To assess the risk of nosocomial transmission of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), we prospectively evaluated a cohort of 531 health care workers. One hundred fifty of these employees reported percutaneous or mucous membrane exposures to blood or body fluids from a patient with the acquired immunodeficiency syndrome (AIDS) during the treatment of 238 such patients since 1981. None of these 150 employees had serologic evidence of HTLV-III/LAV infection on follow-up from 6 to 46 months after exposure. Of the 150, 46 were studied immunologically and 29 had lymphocytes cultured for HTLV-III/LAV. Results of all studies were normal. Of the 531 employees, 3 (0.56%) had serologic evidence of HTLV-III/LAV infection. All were seropositive at the time of study entry; none reported adverse nosocomial exposures. All acknowledged membership in one or more established risk groups for AIDS. This study provides strong evidence that the risk of nosocomial transmission of HTLV-III/LAV is extremely low.