The maturation of naive CD4 T cells into interleukin (IL)-4-producing effectors was shown to require the presence of IL-4 at priming, the cellular origin of which remains unclear. We demonstrate here that naive T cells themselves release IL-4 at very low levels that are nevertheless sufficient to promote their development into Th2-like cells. This conclusion is based on three observations: (1) highly purified human naive CD4 T cells, of neonatal or adult origin, develop into Th2 effectors upon repetitive cycles of stimulation with anti-CD3 monoclonal antibody (mAb) cross-linked to CD32-B7 transfected L fibroblasts followed by IL-2 expansion; (2) IL-4 protein is readily detectable in the concentrated supernatant fluids of priming cultures performed in the presence of anti-IL-4 receptor mAb; and (3) addition of anti-IL-4 or anti-IL-4 receptor mAb at priming markedly inhibits the acquisition of IL-4- and IL-5-producing capacity while enhancing that of interferon-gamma.