The pharmacological effects of cabergoline, a novel ergot alkaloid, against parkinsonism were assessed by comparing its effects with those of bromocriptine and pergolide. The affinities of cabergoline and pergolide for the D2 receptor were about the same, about 7 times stronger than that of bromocriptine. The affinity of each compound for the D1 receptor was markedly lower than its affinity for the D2 receptor. However, other data suggest that cabergoline and pergolide would have D1-receptor agonist activity, whereas bromocriptine would act as a D1-receptor antagonist. In MPTP-lesioned parkinsonian monkeys, cabergoline improved motor disability, and its effect lasted longer than those of bromocriptine and pergolide. Moreover, cabergoline induced no behavioral abnormalities even though at the highest dose used, in contrast to bromocriptine and pergolide, both of which induced hyperactivity. This beneficial effect of cabergoline did not attenuate on prolonged administration. Combined treatment with a low dose of L-dopa and a low dose of cabergoline improved motor disability without inducing the hyperactivity and dyskinesia seen during treatment with L-dopa alone at high doses. From these results, we suggest that cabergoline promises to be a useful anti-parkinsonian agent with a long lasting effect that survives prolonged administration and without the side effects induced by L-dopa.