In this study the combined effect of prostaglandin E2 (PGE2) and interleukin-1 (IL-1) on the proliferation of concanavalin A (Con A) stimulated mouse spleen lymphocytes was studied. IL-1 in concentrations ranging from 0.5 to 5.0 U/ml consistently and significantly enhanced Con A activity. However, to be effective, IL-1 needed to be added at the time of initiation of the culture. If added 24 h later, IL-1 failed to enhance the proliferative response. PGE2 at concentrations ranging from 0.1 to 5.0 ng/ml effectively inhibited or antagonized this enhancing effect of IL-1, with the majority of this IL-1 augmentation abrogated by 5.0 ng/ml PGE2. Unlike IL-1, PGE2 was as effective if added 24 h after initiation of the culture as if added simultaneously with IL-1. PGE2 was also found to markedly suppress the enhanced production of IL-2 resulting from the addition of IL-1 to Con A stimulated lymphocytes, however, the amount of IL-2 produced in the cultures containing both IL-1 and PGE2 was always greater than that produced in the cultures which contained only PGE2. This finding indicates that IL-1 could partially reverse or antagonize the suppressive effect of PGE2 on IL-2 production. In addition, PGE2 at concentrations of 1.0 and 5.0 ng/ml was also found to inhibit the proliferation of IL-2 stimulated cultured T lymphocytes, but by only about 15-20%. The addition of IL-1 to these cultured T cells neither altered the response of the culture T cells to IL-2 nor altered the sensitivity of these cells to PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)