Because HIV-1 infected infants with rapid progression (RP) of disease might benefit from early and intense antiretroviral therapy, the identification of predictive factors of RP becomes extremely important. Currently, the best predictive factors of RP in HIV-1 infected children are HIV-1 RNA levels and CD4-positive T-cell counts. A decrease in CD3-positive T-cell count has been identified as a predictive factor of AIDS development in HIV-1 infected adults. Our objective was to evaluate decreased number of CD3-positive T-cells as a predictive factor of RP in infants. Peripheral blood lymphocytes from HIV-1 infected infants (up to 6 months of age) were analyzed for an association of lymphocyte subsets with RP, which was defined as the occurrence of AIDS or death before 18 months of age. In infants with RP (n = 32), CD3-positive T-cell counts were 3093 cells/microL at <1 month of age, 3092 cells/microL at 1 to 3 months, and 2062 cells/microL at 3 to 6 months. Non-RP infants (n = 49) maintained their CD3-positive T-cells counts at approximately 4000 cells/microL for at least 6 months of life. CD3-positive and CD4-positive T-cell counts were significantly associated with RP. Our results suggest that a decreased CD3-positive T-cell count may be used to predict RP in HIV-1 infected infants (RR = 2.16, P =.001).