The effect of L-threo-DOPS on the reserpine-induced ptosis in mice and its modification by imipramine, a norepinephrine (NE) uptake inhibitor, or nialamide, a monoamineoxidase inhibitor, were studied. Intraperitoneal (i.p.) injection of L-threo-DOPS (800 mg/kg) significantly reduced the severity of the ptosis. This reversal of the ptosis by L-threo-DOPS was markedly potentiated by i.p. injection of either imipramine (2.5 mg/kg) or nialamide (30 mg/kg). Response to L-threo-DOPS was also significantly potentiated by intracerebroventricular (i.c.v.) injection of imipramine (10 micrograms). On the other hand, this treatment with imipramine (10 micrograms, i.c.v.) also significantly potentiated the reversal of the ptosis by NE (20 micrograms, i.c.v.), but the reversal by the subcutaneous (s.c.) injection of NE (1 and 3 mg/kg) was not affected. Reserpine (5 mg/kg, i.p.) markedly decreased the brain content of NE in mice, whereas L-threo-DOPS (400 mg/kg, i.p.) slightly restored it. Moreover, by the pretreatment with nialamide (30 mg/kg, i.p.), L-threo-DOPS produced a significant increase in the brain content of NE in reserpine-treated mice. These results suggested that L-threo-DOPS was capable of reversing the reserpine-induced ptosis due to the formation, at least in part of (-)-NE at the synaptic sites of central noradrenergic neurons.