We report here the results of our study of the carbonic anhydrase inhibitor acetazolamide on cerebral vascular and metabolic function, correlated with the effects of this agent on systemic arterial blood gases and pH. We found that the effects of acetazolamide were to increase PaO2, decrease bicarbonate ion concentration and decrease pH. While these effects were maintained for many hours after both high and low dose acetazolamide, the cerebral metabolic and vascular effects of the drug were transient. The central effects of carbonic anhydrase inhibition were consistent with increased oxygen delivery and increased tissue oxygenation. Hypoxia such as encountered at altitude, represents a challenge to the mechanisms which control blood flow in the brain. The decreased arterial oxygen content at altitude is a ventilatory drive which has the effect of 1) increasing somewhat the PaO2; 2) decreasing the PaCO2; 3) alkalinizing the blood. The decreased PaCO2 then leads to decreased CBF compounding the problem of hypoxemia. In this situation, increasing CBF helps to relieve the tissue hypoxia. This has been done by either increased inhalation of CO2 (Harvey et al., 1988) or by acetazolamide (Cain and Dunn, 1966; Forwand et al., 1968). A common feature in both treatments might be increased tissue CO2 retention (Kjällquist et al., 1969; Meyer et al., 1961) and tissue acidification (Heuser et al., 1975). The two treatments are not identical since acetazolamide seems to have additional effects on cerebral metabolism that elevated CO2 does not. Thus, we can deduce that the primary pathologic effects of acute hypoxia are due to the decreased cerebral blood flow produced by hyperventilation-induced hypocapnia.(ABSTRACT TRUNCATED AT 250 WORDS)