Effective prophylaxis for infection with the human immunodeficiency virus (HIV) is important for health care providers at risk for exposure to infected blood. The average risk from percutaneous exposure is approximately 0.3%, but exposures involving a high titer of HIV or a large volume of infections material are apt to be much riskier. A convergence of indirect evidence strongly suggests that chemoprophylaxis with zidovudine after exposure to HIV may be efficacious. Treatment with zidovudine after percutaneous exposure appears to reduce the odds of infection by almost 80%. Zidovudine prophylaxis effectively prevents perinatal HIV transmission, and treatment during acute retroviral infection may attenuate HIV disease. Reports of "aborted" HIV infection among health care providers who have been stuck with contaminated needles suggest that antiretroviral treatment in the window of opportunity after exposure to HIV could prevent virus propagation and allow local cutaneous host defenses to clear the infection. Although efficacy has not been shown in controlled clinical trials, these data support a potential benefit from treatment after exposure. It is difficult to define the optimal regiment that should be used for prophyaxis, given the emergence of antiretroviral resistance among source patients. Current recommendations favor the use of zidovudine plus lamivudine for 4 weeks. Use of indinavir or other protease inhibitors is advised when the source patient is likely to harbor resistant virus or when exposure is especially hazardous.