The study of true seronegative HIV-1 infections may have important implications for the diagnosis and prevention of HIV-1 infection. The case of an AIDS patient with persistently negative HIV serology is described. Genetic and phylogenetic analysis indicated that she was infected with A2 subsubtype HIV-1 transmitted by her seropositive and asymptomatic sexual partner. The clinical and serological discordant results suggest the presence of an immunological deficiency that prevents the formation of HIV-1-specific antibodies.