Platelet activating factor (PAF) is a highly potent phospholipid mediator known to be active in many biologic systems. To date little is known of the effect of PAF on B lymphocytes. Using three immunoglobulin (Ig)-secreting B-lymphoblastoid lines, we have demonstrated that PAF can influence both early activation and late differentiation events. Following addition of 10(-7) to 10(-11) M PAF, but not the inactive metabolite lyso-PAF, all three cell lines demonstrated rapid, dose-dependent increases in free cytosolic Ca2+ concentrations ([Ca2+]i). The changes in [Ca2+]i resulted from release of intracellular stored Ca2+ as well as transmembrane Ca2+ uptake. In parallel PAF caused significant alterations in the kinetics of Ig secretion in the Ig-secreting lymphocyte lines. A 6-12-fold increase in Ig production was detectable after 24 h of stimulation with PAF, which was followed by a plateau over the next 48 h. All of these events were inhibited by the specific PAF antagonists Web2086 and CV3988. PAF antagonists themselves had a profound effect, diminishing Ig production by the B-cell lines by up to 90%. These data indicate that PAF may have an important immunomodulatory role in B lymphocytes.