The open-field test was used to study the involvement of serotonergic and dopaminergic mechanisms in the action of lisuride on locomotor activity in the rat. Lisuride produced a biphasic locomotor effect. The maximum locomotor stimulatory response of lisuride was stronger than that of apomorphine and comparable with that of apomorphine and LSD combined. Hypermotility induced by high doses of lisuride was partially suppressed by the serotonin antagonist cyproheptadine and not further enhanced by LSD. A moderate dose of lisuride potentiated apomorphine-induced hypermotility in the same manner as has been shown for LSD. Lesion of dopaminergic structures within the median raphe nucleus by 6-OHDA produced a potentiation of lisuride-induced hypermotility. This effect was suppressed by cyproheptadine. The locomotor inhibitory effect of low doses of lisuride may be related to a stimulation of presynaptic mesolimbic dopamine receptors. It is concluded that the locomotor stimulant effect of higher doses of lisuride may depend on stimulation of postsynaptic dopamine receptors and a serotonergic action and that the locomotor effects of lisuride reflect a complex interaction at dopaminergic and serotonergic transmission systems.