Since the nitric oxide (NO) and cyclooxygenase pathways have been suggested to have important roles in most vasodilations, our aim was to study the influence of cyclooxygenase inhibitors and nitrovasodilators on cerebrovascular reserve capacity. Corticocerebral blood flow was measured by hydrogen polarography during hypercapnia and acetazolamide stimuli in conscious rabbits. The measurements were repeated in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin as nitric oxide synthase (NOS) and cyclooxygenase inhibitors. The effects of nitroglycerin and isosorbide-5-nitrate were also tested. L-NAME completely, while indomethacin markedly inhibited the hypercapnic corticocerebral blood flow response. Nitroglycerin and isosorbide-5-nitrate significantly attenuated hypercapnia elicited corticocerebral blood flow increase. The different treatments reduced only moderately the acetazolamide-induced corticocerebral blood flow response. These results lend support to the hypothesis that antithrombotic and antiinflammatory medication (cyclooxygenase inhibitors) and nitrovasodilator treatments could interfere with the measurement of cerebrovascular reactivity resulting in underestimation of the cerebrovascular reserve capacity in patients taking these drugs.