We determined HIV infections in the Rakai cohort before (82/9434) and after (131/13082) the availability of antiretroviral therapy (ART). The proportions of total HIV infections pre-ART and post-ART were 18.3% and 13.7%, respectively, among identifiable HIV-discordant couples, 23.2% and 26.0%, respectively, in concordant HIV-negative couples, 29.3% and 17.6% in married persons with unknown partner status, and 29.3% and 42.7% in the unmarried. Voluntary counseling and testing targeting discordant couples is unlikely to have a substantial impact in this setting.