The capacity of the ergoline, pergolide, and of the partial ergoline, LY 141865, to stimulate pre- and postsynaptic dopamine (DA) receptors was investigated. Binding studies have revealed that pergolide has a high affinity, while the partial ergoline, LY 141865, has a low affinity for the postsynaptic striatal DA receptors in vitro. Two behavioral animal models were used to assess the DA agonist potencies of these compounds for the postsynaptic DA receptors in vivo. Pergolide induced turning behavior in rats with 6-hydroxydopamine (6-OH-DA) lesions, and relief of tremor in monkeys with ventromedial tegmental lesions, at a lower dose and for a longer duration than LY 141865. An in vivo and an in vitro biochemical test was use to measure the ability of these compounds to stimulate presynaptic DA receptors. In the in vitro test, pergolide and LY 141865 were found to have low inhibitory activity for synaptosomal tyrosine hydroxylase, while in the in vivo test, both drugs were effective even in low doses in reversing the gamma-butyrolactone elicited increased accumulation of striatal DOPA. These results suggest that pergolide has a high affinity for pre- and postsynaptic DA receptors, while its partial ergoline analogue has a high affinity for the presynaptic, but not for the postsynaptic DA receptors. The data also suggest that dopamine synthesis in vitro and in vivo may be regulated by different presynaptic DA receptors.