Rats were injected with one of five drugs alleged to inhibit brain prostaglandin (PG) synthesis: indomethacin, diclofenac, naproxen, aspiring and paracetamol. Animals were killed after 30 min. and the endogenous formation of PGF2alpha and PGE2 in brain homogenates was measured by mass fragmentography using deuterium labelled PGF2alpha and PGE2 as internal standards. Diclofenac, indomethacin, and naproxen inhibited dose dependently, the synthesis of PGF2alpha. The ED50 for diclofenac was 0.4 mg/kg, for indomethacin 1 mg/kg and for naproxen 2 mg/kg. In equieffective doses indomethacin had the longest duration. The time taken for the inhibition to decline to half its maximal value was 32 hrs for indomethacin and about 15 hrs for diclofenac and naproxen. Under the present conditions aspirin and paracetamol failed to produce significant reduction of PG synthesis in the rat brain homogenates in doses up to 100 mg/kg.