Human immunodeficiency virus type 1 (HIV-1)-specific T cell responses were characterized in a blinded study involving infected individuals and their seronegative exposed uninfected (EU) partners from Lusaka, Zambia. HIV-1-specific T cell responses were detected ex vivo in all infected individuals and amplified, on average, 27-fold following in vitro expansion. In contrast, no HIV-1-specific T cell responses were detected in any of the EU partners ex vivo or following in vitro expansion. These data demonstrate that the detection of HIV-1-specific T cell immunity in EU individuals is not universal and that alternative mechanisms may account for protection in these individuals.