Previous work by the authors has established decreased brain ATP concentration after a combined hypoxic-hypotensive episode. This study was undertaken to determine what changes, if any, occur in brain norepinephrine (NE), dopamine (DA), and serotonin (5HT) concentration in association with hypoxia and hypotension, and to correlate any observed changes with simultaneously measured ATP concentrations. Rats were subjected to a 30-minute period of hypoxia (F102 = 0.075) and hemorrhagic hypotension (MAP = 30 mm Hg) and then resuscitated. Significant increases (P less than .05) in cortical 5HT were observed at a time when ATP concentration was significantly (P less than .005) reduced. Additional experiments were conducted on rats depleted of 5HT by prior treatment with 5,7-dihydroxytryptamine. Equal decreases in ATP concentration were measured, and the cardiovascular response to hypoxic hypotension in 5HT-depleted rats was similar to that in 5HT-intact rats. We conclude that the increased 5HT after hypoxic hypotension does not cause the decreased ATP concentration, nor does 5HT play a major role in cardiovascular homeostasis under the conditions of this experiment.