The effect of a new synthetic ergot alkaloid, pergolide mesylate, on the inhibition of PRL during 24-h periods was evaluated in four rhesus monkeys and three patients with Parkinson's disease. In the monkeys, the mean PRL level during the 24-h period fell to 24% of control in response to 50 jug pergolide daily and to 6.6% of control with 200 μg. With 1000 μg pergolide daily, PRL was unmeasurable in the great majority of samples over 24 h. In addition, the marked episodic fluctuation in PRL occurring in controls was not observed in treated animals. In three patients with Parkinson's disease, treatment with pergolide also resulted in uniform 24-h suppression of PRL. In one patient on pergolide (100 μg/day), the mean 24-h PRL level fell to 18% of control, and in two other patients on 200 and 600 μg pergolide, respectively, whose mean PRL levels were 4.1 and 7.4 ng/ml, respectively, before treatment, no PRL was detected in any of the blood samples obtained during the 24-h periods. These data provide evidence that pergolide is a potent inhibitor of PRL in rhesus monkeys and in patients with Parkinson's disease; the effect is uniform over 24-h periods. © 1980 by The Endocrine Society.