Serotonergic and adrenergic receptors were examine in rat brains by direct binding assays after chronic treatment with tricyclic antidepressants. Chronic amitriptyline (AMT) treatment (10 mg/kg/day i.p. for 21 days) decreased specific 3H-spiperone binding in the cortex and not in the caudate nuclei. Specific 3H-dihydroalprenolol (3H-DHA) binding was reduced in cerebellar but not in cerebral cortex. Chronic desipramine (DMI) treatment given in the same dose schedule, on the other hand, decreased specific 3H-DHA binding in both cerebellar and cerebral cortex. Specific 3H-spiperone binding in the cerebral cortex was also reduced but to a lesser extent than that in the AMT treated group. Scatchard analysis showed that reductions in 3H-spiperone or 3H-DHA binding in all cases were due to decreases in number of binding sites (Bmax) and not to changes in dissociation constants (KD). No change was observed in 3H-serotonin (3H-5HT), 3H-clonidine, or 3H-WB-4101 binding. The results show that there is no single common change in brain adrenergic and serotonergic receptors after chronic AMT and DMI treatment.