Human naive CD4(+) T helper (Th) and CD8(+) cytotoxic (Tc) T cells, which only produce IL-2, may differentiate into Th1/Tc1 or Th2/Tc2-like lymphocytes, characterized by their cytokine production profile. 1alpha,25-dihydroxyvitamin D-3 (1alpha,25(OH)(2)D-3) has been reported to inhibit Th1/Tc1-related, but increase Th2/Tc2-associated cytokines in T cells from adults. In industrialized countries, vitamin D supplementation for prevention of rickets is initiated within the first days of life and continued throughout the entire first year. Epidemiologic studies suggest an association of vitamin D exposure in newborns with the incidence of allergic diseases in later life. This study addresses the effects of 1alpha,25(OH)(2)D-3 on Th1/Tc1 versus Th2/Tc2 differentiation in long term cell cultures of (naive) cord blood T lymphocytes. Our results show that in CD4(+) as well as CD8(+) cord blood cells, 1alpha,25(OH)(2)D-3 inhibits not only IL-12-generated IFN-gamma production, but also suppresses IL-4 and IL-13 expression induced by IL-4. Thus, in cord blood 1alpha,25(OH)(2)D-3 induces a T cell population without predominance of Th2 related cytokines.