Two potent inflammatory mediators, interleukin 1 (IL-l) and tumor necrosis factor (TNF) as well as lipopolysa~ha~de (LPS) increased group II phospholipase 4 (PL4) mRNA levels, which resulted in enhanced secretion of the PL4 enzyme from rat smooth muscle cells. CAMP-elevating agents also stimulated the release of PL4 and increased the mRNA, but IL-I, TNF and LPS did not affect CAMP levels. Furthermore, the effects of TNF and CAMP-elevating agents were not additive but synergistic. Therefore, we concluded that the level of rat group II PL4 mRNA is controlled at least by two distinct mechanisms, one involves CAMP and the other is mediated by TNF, IL-l and LPS. This study also suggests important roles of group II PLA, in pathogenesis of vascular inflammation.