Anti-inflammatory glucocorticoids inhibit prostaglandin (PG) biosynthesis by preventing arachidonic acid release from phos-pholipids rather than inhibiting the cyclooxygenase^1–16. As in other cells^17–19, this steroid action depends on receptor occupation and de novo protein/RNA biosynthesis^12–16. We have previously shown in guinea pig perfused lungs and rat peritoneal leukocytes that the effect of steroids on PG generation is mediated by an uncharacterized ‘second messenger’^13,16. Now, we report that this factor (which we have named ‘macrocortin’) is an intracellular polypeptide whose release and synthesis are stimulated by steroids. Macrocortin derived from rat peritoneal leukocytes is very similar to that released from guinea pig lungs.