The purpose was to ascertain risk factors for HIV infection in a predominantly rural population using descriptive epidemiologic studies performed at a university health sciences center. Participants included adult patients with HIV infection or AIDS who were cared for between January 1982 and January 1993. The relative frequency of cases in minority and female heterosexual patients increased significantly. The male to female ratio among blacks with HIV infection declined to 1.1:1 during the final 3 years of the study. Patients who believed they had acquired infection in Virginia were more likely to cite a rural area of acquisition and to have had multiple heterosexual partners but were less likely to have had male homosexual contact than patients who believed they had been infected in other states. HIV continued to spread into rural areas of Virginia, and the gender ratio among blacks with HIV declined throughout the study. Having multiple heterosexual partners, the main risk factor for HIV transmission worldwide, may now result in HIV infection in rural Virginia.