THE Flinders Sensitive Line (FSL) rats have been proposed as a genetic animal model of depression because their innately high immobility in the forced swim test is counteracted by antidepressants. This model was used to test the acute and chronic effects of two novel compounds which have either an agonist or antagonist-like effect at melatonin receptors. In the acute study FSL and control Flinders Resistant Line (FRL) rats were unaffected by either the agonist S 20304 (1 or 20 mg/kg) or the antagonist S 20928 (1 or 10 mg/kg) given 1 h prior to a single 5 min swim test. In the chronic study a reduction in immobility in the FSL rats at the highest dose of the agonist was the only significant drug effect. These findings suggest that the melatonin receptor agonist S 20304 may have antidepressant potential.