OUR discovery that aspirin-like drugs inhibit the biosynthesis of prostaglandins^1–3 led to the proposal that this was their main mechanism of action^1,4. Several observations have added force to the theory. These include the correlation between relative potencies as prostaglandin synthetase inhibitors in vitro and anti-inflammatory activity in vivo^5–7, the generality of the inhibition in many species and preparations⁸, and the demonstration of release of prostaglandins in inflammation^9,10 and fever^11,12. In addition, prostaglandins of the E series cause an inflammatory response in the skin of rats and man^13,14 and a fever in cats^15,16 and man¹⁷.