To examine rates of and risk factors for heterosexual transmission of human immunodeficiency virus (HIV), the authors conducted a prospective study of infected individuals and their heterosexual partners who have been recruited since 1985. Participants were recruited from health care providers, research studies, and health departments throughout Northern California, and they were interviewed and examined at various study clinic sites. A total of 82 infected women and their male partners and 360 infected men and their female partners were enrolled. Over 90% of the couples were monogamous for the year prior to entry into the study; < 3% had a current sexually transmitted disease (STD). The median age of participants was 34 years, and the majority were white. Over 3,000 couple-months of data were available for the follow-up study. Overall, 68 (19%) of the 360 female partners of HIV-infected men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male partners of HIV-infected women (95% CI 0.3-8.5%) were infected. History of sexually transmitted diseases was most strongly associated with transmission. Male-to-female transmission was approximately eight-times more efficient than female-to-male transmission and male-to-female per contact infectivity was estimated to be 0.0009 (95% CI 0.0005-0.001). Over time, the authors observed increased condom use (p < 0.001) and no new infections. Infectivity for HIV through heterosexual transmission is low, and STDs may be the most important cofactor for transmission. Significant behavior change over time in serodiscordant couples was observed.