The present study investigated the metabolism of serotonin (5-HT) in rats made hypertensive by treatment with DOCA/NaCl. 5-Hydroxytryptamine and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were significantly elevated in a number of regions of the brain in rats treated for 2 weeks with DOCA/NaCl. Elevations in levels of 5-HIAA were present with 4 weeks of treatment with DOCA/NaCl but levels of 5-HT were not altered. No changes in the metabolism of 5-HT were detectable with 5 weeks of treatment with DOCA/NaCl. Levels of tryptophan were also elevated in a number of regions of the brain by treatment with DOCA/NaCl. Alterations in norepinephrine (NE) in the brainstem were present with 2, 4 or 5 weeks of treatment with DOCA/NaCl. The neurochemical effects of muscimol, a GABA agonist, were also investigated in rats treated with DOCA/NaCl for 4 weeks. Significant increases in levels of 5-HIAA and 5-HT were present in rats treated with DOCA/NaCl but not in controls, 15 min after intra ventricular administration of muscimol (1.0 μg/300g body weight). Sixty min after muscimol, 5-HIAA was increased in both rats treated with DOCA/NaCl and control rats, but 5-HT was only increased in the hypothalamus. Treatment with DOCA/NaCl produced changes in the metabolism of 5-HT that may be important in the genesis of hypertension, but are not required for the maintenance of elevated arterial pressure. A disturbance ofGABA-5-HT interactions between GABA and 5-HT in brainstem sites may also contribute to the pathogenesis of hypertension induced by DOCA/NaCl. © 1988.