The Wet-Dog shake (WDS) response was correlated in rats to central 5-hydroxytryptamine (5HT) activity. Rats (200-250 g) were injected s.c. with 5-hydroxytryptophan (Cambrian, 25-200 mg/kg) (5-HTP) 30 min after carbidopa (merck-USA, 25 mg/kg i.p.). Other rats received L - tryptophan (Koch-Ligh Light, 25-100 mg/kg i.p.), 30 min after pargyline (Warner, Z5 ma/ kg i.p.), lysergic acid diethylamide (LSD, Sandoz, 0.05-1 mg/kg .p.), 5-methoxy-N,N - dimethyltryptamine (5-MeODMT, Sigma, 0.1-4 mg/kg i.p.), quipazine (Miles, 1.5-50 mg/kg i.p.), chlorimipramine (CIBA-Geigy) (5-40 mg/kg i.p.), ORG 6582 (Organon, 1-40 ma/ kg i.p.) or femoxetine (FG 4963, Ferrosan 1-40 mg,/kg). Other rat were pretreated withcarbidopa and 5-HTP (100 mg/kg) and inject 90 min later apomorphine (Evans, 0.5 mg/kg s.c.), dexamphetamine (SK+F, 4 mg/kg i.p.), haloperidol (Searle, 2 mg/kg i.p.), clonidine HCl (Boehr.Ingelheim, 0.5 mg/kg i.p.), propranolol HCl (ICI, 10 mg/kg i. p.), harmaline (3 mg/kg i. p. ), methysergide (5 ma/ kg i.p.), cyproheptadine (10 mg/kg i.p.), atropine (5 mg/kg i.p.), scopolamine (3 mg/kg i.p.), physostigmine (eserine, 0.3 mg/kg .p.) or arecoline (5 mg/kg i.p.). The incidence of WDS was noted and the concentrations of 5-HT in various areas of the brain were determined. 5-HTP caused a WDS response in a dose-dependent manner up to 150 mg/kg. Methysergide briefly (1 hr) suppressed, and cyproheptadine completely inhibited, the WDS response. L - tryp-tophan and pargyline, LSD, 5-MeODMT and quipazine all produced VDS. Femoxetine caused mild hyperactivity, ORG 6582 caused some WDS and chlorimipramine had no effect. Apomorphine, am-phetamine, haloperidol, propranolol, clonidine, harmaline, atropine, scopolamine, arecoline and physostigmine all failed to produce WDS. Only apomorphine and amphetamine produced significant in-hibition of the 5-HTP induced WDS response. Administration of 5-HTP caused a parallel increase in 5-HT levels in all regions of the CNS (thalamus, hypothalamus, midbrain, hippocampus, brainstem, cerebellum, spinal-cord, striatum, etc.). Bilateral destruction of the globus pallidus had no effect on the WDS response to 5-HTP; neither did section at the level of the anterior commissure. Section at the level of the caudal diencephalon tended to reduce the WDS response and section at the level of the posterior commissure line virtually abolished it.