Prostaglandins of the E series (PGE) have traditionally been considered as suppressive for immune responses; however, recent data suggest that PGE channels the immune response towards a T helper 2 type response and production of selected immunoglobulin isotypes. Herein, we present data showing that PGE(2) and other agents that induce intracellular rises in cAMP significantly increased B lymphocyte IgG1 production (up to sevenfold). PGE(2) acted on small resting B cells and on uncommitted B cells expressing high levels of surface IgM to increase the number of cells secreting IgG1. PGE(2) even increased IgG1 synthesis by purified B cells in the absence of exogenous IL-4. Finally, PGE(2) synergized with IL-4 to induce germline gamma1 transcripts through the switch region. This transcription is required for isotype switching. These data support the hypothesis that PGE(2) acts on uncommitted resting B cells at the level of germline gamma1 transcription to promote class switching to IgG1. PGE(2) is an important regulator of the immune response, shifting the balance towards a T helper type 2 response, directing selection of the isotypes produced, and promoting memory cell formation.