1. The calcium ionophore, A23187, stimulated leukotriene B4 (LTB4), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) synthesis by 4 day carrageenin-elicited rat peritoneal macrophages. 2. At concentrations of 2 x 10(-7)-2 x 10(-5) M indomethacin and aspirin enhanced A23187-stimulated LTB4 synthesis and inhibited PGE2 and TXB2 formation. 3. PGE2 inhibited A23187-stimulated LTB4 and TXB2 formation as well as the augmentation of LTB4 release caused by aspirin and indomethacin. However, PGE2 was ineffective when the cells were challenged with arachidonic acid (AA). 4. Dibutyryl adenosine 3':5'-cyclic monophosphate (db-cyclic AMP) partially inhibited A23187-stimulated LTB4 production. 5. Our results suggest that PGE2 inhibits macrophage LTB4 synthesis by limiting the availability of AA. Indomethacin and aspirin, possibly by removing the regulatory effect of PGE2, promote the synthesis of the pro-inflammatory LTB4.