PURPOSE: To update ophthalmologists on recent developments in the area of antiviral chemoprophylaxis after occupational exposure to human immunodeficiency virus (HIV). Background information is provided by which to make an informed decision about whether to initiate antiviral chemoprophylaxis against HIV infection. METHODS: We discuss why HIV postexposure prophylaxis should be considered; when prophylaxis should be initiated; where prophylaxis medications should be located in the operating or emergency room; and what medications might be used and the factors influencing their selection. Recent provisional recommendations by the United States Centers for Disease Control and Prevention and the International AIDS Society-USA are reviewed along with literature dealing with antiviral chemoprophylaxis against HIV infection. RESULTS: Recommendations are made for specific antiviral chemoprophylaxis after occupational exposure to HIV based on the Centers for Disease Control and Prevention and the International AIDS Society-USA provisional recommendations. Uncertain areas and the minor discrepancies in these two reports are discussed. CONCLUSIONS: Prevention of HIV transmission after accidental occupational exposure is possible. Combination therapy is more effective than monotherapy in treating HIV infections. Zidovudine (AZT or ZDV) is effective in postexposure prophylaxis; the combination of zidovudine and lamivudine (3TC) and indinavir (IDV) has greater antiretroviral activity than zidovudine alone does. The requirements for effective HIV postexposure prophylaxis may be somewhat different than those for optimum HIV treatment in the chronically ill HIV-positive patient. Ophthalmologists should have an in-depth knowledge of current thinking regarding HIV pathophysiology and treatment.