To investigate if serial measurement of T helper (CD4) lymphocyte number in peripheral blood is of prognostic value, we determined lymphocyte function in asymptomatic and symptomatic HIV antibody positive and negative homosexual males and related the results to absolute number of CD4 lymphocytes in peripheral blood. Lymphocyte function was determined by measuring streptolysin O (SLO)-induced proliferative responses of peripheral blood lymphocytes (PBL) and of PBL depleted of CD8 lymphocytes. Phytohemagglutinin (PHA) induced interleukin-2 (IL-2) production was also measured. In all functional tests values were significantly lower in HIV antibody-positive subjects than in HIV antibody-negative subjects. Results lower than the 95% confidence limit in HIV antibody-negative individuals were therefore defined as "decreased." Decreased functional responses were most frequent (83-100%) in individuals with a number of CD4 lymphocytes of less than 400/microliters, and were least frequent (3-21%) in subjects with a CD4 lymphocyte count of greater than 600/microliters. Frequency of decreased functional responses was intermediate in the population with 600-400/microliters CD4 lymphocytes. The magnitude of functional responses differed significantly between groups with less than 400, 400-600, and greater than 600 CD4 lymphocytes per microliter, indicating that T helper cell number decreases with loss of immune function.