The effect of amphetamine (AMPH) on plasma corticosterone was studied in the conscious, unstressed rat. AMPH (0.5-5.0 mg/kg) produced a dose-dependent increase in plasma corticosterone. This rise in plasma corticosterone was not altered by the adrenergic blocking agents phenoxybenzamine or propranolol. In contrast, the serotonergic depleting agent p-chloroamphetamine significantly inhibited the AMPH-induced rise in corticosterone. In addition, the serotonergic blocking agent methysergide, but not cyproheptadine, inhibited the corticosterone increase induced by AMPH.