The central action of nomifensine (NF), a new antidepressive drug, was studied in rats and mice. NF stimulates locomotor activity in normal animals as well as in animals whose motor activity has been depressed by reserpine, alpha-methyltyrosine (alpha-MT), bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulfide (Fla-63) or phenoxybenzamine. The sedation produced by alpha-MT plus reserpine or by spiroperidol is not affected by NF. NF induces stereotypy in the rat and antagonizes the catalepsy induced in the rat by neuroleptics, pilocarpine and arecoline. The catalepsy induced by alpha-MT plus reserpine is not influenced. NF elevates the brain levels of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the rat. These and previous results indicate that the profile of action of NF differs both from that of known tricyclic antidepressive drugs and that of dopaminergic stimulants.