Lymph node T cells from naive, 4-day-old neonatal mice resemble activated adult T cells in that they produce low levels of IL-2 but high levels of IL-4 in response to anti-CD3 stimulation in vitro. Herein, we show that the capacity for high level IL-4 production is rapidly lost in the early postnatal period. A decline is first evident at 5 days postbirth. By 6 days postbirth, T cells secrete IL-4 at low levels, similar to those produced by T cells from naive, adult animals. In contrast, the acquisition of high, adultlike IL-2 or IFN-gamma production does not occur until approximately 6 wk of life. Thus, the loss of high level IL-4 production and the acquisition of high level IL-2 and IFN-gamma production are distinct developmental events, occurring at widely separated intervals. There are two phases in the transition to adultlike IL-2 production. In the early neonatal period, the underproduction of IL-2 appears to be due to a combination of intrinsic nonresponsiveness to CD3-mediated stimulation and the production of a soluble inhibitor of IL-2 production. The inhibitory activity required the presence of IL-4 because neutralizing anti-IL-4 antibody completely eliminated inhibition. Moreover, experiments using rIL-4 showed that IL-4 alone was sufficient to dramatically inhibit IL-2 production by T cells from naive, adult animals in a primary stimulation. Between 4 to 5 days and 6 wk of life, the underproduction of IL-2 and IFN-gamma appears to result solely from a lowered responsiveness of the T cells. Thus, the progression to adultlike lymphokine production involves a combination of changes in the types of lymphokines produced and in the magnitude of the response to activation signals.