The predictive value of low T cell reactivity to CD3 monoclonal antibodies for development of AIDS was evaluated and compared with low CD4+ cell numbers and the presence of syncytium-inducing human immunodeficiency virus (HIV) variants in 122 seropositive asymptomatic homosexual men for 4.5 years. Low T cell reactivity was a strong predictor for progression to AIDS in a multivariate proportional hazards analysis using these markers as covariates at entry and as time-dependent covariates. The combination of the three markers was associated with development of AIDS in 6 of 7 men within 15 months. In contrast, the group that lacked any of these markers had a very low risk (11%) for developing AIDS. In groups with one or two of these three markers, progression rates were 33% and 66%, respectively. These data demonstrate that measurement of T cell function in vitro is of value for staging of HIV infection and may be useful for monitoring therapy.