8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective serotonin1A receptor agonist, was studied for its anti-immobility activity in the forced swimming test after different schedules of treatment. Single doses of 0.250 and 0.500 mg/kg 8-OH-DPAT s.c. reduced the immobility time of rats with no effect on open-field activity. Similar results were obtained with a three-injection course of 8-OH-DPAT in 24 h (doses from 0.125 to 0.500 mg/kg s.c.) or with a once daily injection of 0.250 mg/kg s.c. 8-OH-DPAT for 7 or 21 days. Methiothepin 0.2 mg/kg s.c. and 1-propranolol 20 mg/kg s.c. significantly antagonized the anti-immobility effect of three injections of 0.25 mg/kg s.c. 8-OH-DPAT but 2 mg/kg i.p. metergoline had no such effect. The effect of 8-OH-DPAT was also antagonized both by 0.5 mg/kg i.p. haloperidol and 100 mg/kg i.p. sulpiride, and in animals given an intracerebroventricular injection of 150 micrograms 5,7-dihydroxytryptamine to deplete brain serotonin levels. The results show that 8-OH-DPAT, by acting on serotonin neurons in the brain, produces disinhibitory effects in a rat model predictive of antidepressant activity and suggest that serotonin1A agonists such as 8-OH-DPAT could constitute a novel class of rapid-acting antidepressant agents.