We studied cytokine production by stimulated peripheral blood mononuclear cells from 55 HIV-infected children born to HIV-infected mothers, and compared it to that of exposed, but uninfected, age-matched children. Cytokine production was quantified using a commercially available specific ELISA kit. Cell proliferation was evaluated by incorporation of ((3)H) thymidine. A significant defect in type 1 cytokine production of IFN-gamma and IL-2 in HIV-infected children compared to controls was observed, but without a concomitant increase in type 2 cytokines. Indeed, IL-5 production was even lower in HIV-infected children than in controls, the IL-5 decrease being the best predictive marker of immunodeficiency. Furthermore, IL-5 levels were decreased from the early phases of HIV infection, being significantly lower in the clinical category B with respect to controls, and in AIDS with respect to both controls and children in category A. Such a strong correlation with the stage of infection has not been previously described in HIV-infected children. In addition, we found a correlation between SI/X4 viral phenotype and lower IL-5 levels. Our data suggest a dysfunctional cytokine production by PBMC from HIV-infected children as regards both Th1 and Th2 cytokines resulting from quantitative as well as qualitative defects induced by HIV-1.