The current series of experiments were designed to explore the role of the B cell growth factor, interleukin-4 (IL-4), in the age-related decrease in production of antitetanus toxoid antibody in vitro. Exogenous recombinant IL-4 led to significant suppression of antitetanus toxoid antibody synthesis and numbers of antitetanus toxoid antibody-secreting B cells in cultures from healthy old subjects and healthy young subjects. These effects were most pronounced when IL-4 was present during the early phase of culture. Lymphocytes from old subjects were less sensitive to these effects and produced significantly less IL-4 than did lymphocytes from young controls. The addition of exogenous IL-4 may be inhibiting early activation signals that normally stimulate proliferation of B cells. A decreased sensitivity to the growth-promoting effects of IL-4 may be one of the mechanisms underlying defective specific antibody synthesis in aging.