Exposure to human immunodeficency virus (HIV) can result in HIV infection which is defined by seroconversion and the detection of HIV-specific antibodies. Nevertheless, in every cohort at risk for HIV infection, individuals are present in whom seroconversion is not observed despite multiple documented exposures to HIV. Recent studies have shown that HIV-specific T-lymphocytes are present in the peripheral blood of these HIV-exposed seronegative individuals, suggesting that cell-mediated immunity (CMI) could have a protective role in the prevention of HIV infection. In most individuals who seroconvert, HIV infection is followed by a long period of clinically asymptomatic latency which ultimately results in the development of acquired immunodeficency syndrome (AIDS). Although this progression is observed in the majority of HIV-infected individuals, individuals exist who are asymptomatic and have relatively high CD4 counts despite long-lasting HIV infection. Analogous to that observed in seronegative HIV-exposed individuals, strong HIV-specific CMI seems to be characteristic of these HIV-seropositive (HIV+) long-term non-progressors (LTNP). Because strong HIV-specific CMI is present in HIV-seronegative individuals exposed to HIV and in HIV+ LTNP, we believe that HIV-specific CMI may be the main correlate of protection against HIV infection and against the progression of HIV infection to AIDS.