The effect of the pretreatment of human peripheral blood lymphocytes by Prostaglandin E2 (dissolved in medium) on the spontaneous Plaque-Forming Cell generation has been evaluated. A significant enhancement of immunoglobulin production, markedly increased by the addition of further PGE2 to the pretreated cells, has been demonstrated. Experiments carried out with indomethacin have shown an inhibition of plaque formation, thus indicating that the content of endogenous prostaglandin E2 may play an important role in the enhancement of antibody synthesis, previously described. Results obtained with populations of rosetting and non-rosetting lymphocytes pointed out that non-rosetting cells are exclusively responsive to prostaglandin treatment.