The infectiousness of the index case and the susceptibility of the exposed host mediate the sexual transmission of human immunodeficiency virus (HIV). Infectiousness of the index case is determined by the inoculum of HIV and viral factors that favor transmission. Persons with primary infection, late stage disease, or low CD4 counts appear to transmit HIV with greater efficiency, presumably through increased viral burden in genital secretions. Susceptibility to HIV infection is determined by hereditary resistance factors, acquired immunity, site of exposure to the virus, and integrity of local barriers (e.g., vaginal epithelium). Hereditary resistance factors, such as cell surface receptors required for transmission of some viral variants, have been identified in studies of exposed, but uninfected persons. Acquired immunity, including protective cytotoxic T lymphocyte or antibody responses, may be important in persons repeatedly exposed to HIV who do not become infected. Sexual practices also affect susceptibility, with receptive anal intercourse having the highest risk, followed by vaginal intercourse and fellatio. Similarly, women are more susceptible to infection than men, through vaginal intercourse. In general, any factor affecting excretion of HIV or the number of receptive cells can be expected to affect the efficiency of transmission.