The Multicenter AIDS Cohort Study (MACS) was designed to study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, including the relationship between hepatitis B virus (HBV) and HIV-1 infection. In total, 4954 homosexual men were recruited from April 1984 through March 1985 and have been followed up thereafter every 6 months. Hepatitis B surface antigen and hepatitis B core antibody were tested for at the first visit by RIA or EIA; HIV-1 antibody testing was done at each visit by ELISA and confirmed by Western blot assay. The role of HBV infection in HIV-1 seroconversion was studied by stratification for sexual behavior and disease visit by visit. The adjusted risk ratio was 2.02 for hepatitis B surface antigen carriers and 2.14 for hepatitis-immune cases compared with hepatitis B-susceptible subjects. Similar results were obtained using a logistic regression model. After taking into account changes in sexual behavior and disease over time, the authors conclude that past HBV infection remains suspect as a cofactor or as a surrogate for other factors associated with HIV-1 seroconversion.