AIMS: We investigated the effect of several Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), on the preoptic nerve oxygen tension (ONPO2), as indomethacin previously has demonstrated a strong decreasing effect on ONPO2. We tested whether these NSAIDs, like indomethacin, also reduce the increasing effect of dorzolamide on ONPO2. METHODS: ONPO2 was measured 0.5 mm above the optic disc in 23 domestic pigs (26-36 kg) with a polarographic oxygen-sensitive electrode. One of the following NSAIDs was administered intravenously as increasing doses or as one large dose: indomethacin, ibuprofen, diclofenac, ketoprofen, parecyclo-oxygenase-2 inhibitor and lornoxicam. Indomethacin was both tested alone and after preceding administration of the other NSAIDs. Dorzolamide was also tested after preceding administration of NSAIDs different from indomethacin. RESULTS: Indomethacin decreased ONPO2 significantly in a dose-dependent manner. None of the other NSAIDs produced any effect on the ONPO2 (p>>0.05; n = 17). No difference was found between the effect of indomethacin injected alone, and after preceding administration of the other NSAIDs. Intravenous dorzolamide (500 mg) increased ONPO2 by 32 (7)% (n = 7; p<0.001) after preceding administration of several NSAIDs different from indomethacin. CONCLUSIONS: Indomethacin decreased ONPO2, while the other NSAIDs showed no effect on ONPO2, and they did not affect the effect of indomethacin. The hypoxic effect of indomethacin must be due to another mechanism than cyclo-oxygenase inhibition. The effect of dorzolamide on ONPO2 is not related to prostaglandin production.