The intravenous infusion of prostaglandin (PG) E1, E2, and A1 into normal rats at a dose of 2 μg/min significantly lowered plasma insulin levels with a tendency to recovery in the post-infusion period. Whereas PGA1 infusion resulted in a moderate but significant hypoglycaemia, the administration of E-series PGs always produced a hyperglycaemic effect. The interference of PGE1 on insulin response to classical insulinogogues (glucagon, aminophylline, and tolbutamide) was also investigated. The results of these experiments demonstrate that PGE1 exerts an inhibitory action on insulin response to all insulin releasing agents investigated. As regards the haemodynamic effects of PGs, PGE1 and PGE2 lowered the arterial blood pressure by about 20%, while PGA1 was almost completely ineffective. On the other hand, the lowering effect of PGE1 on circulating insulin levels remained unchanged in rats treated with reserpine. These findings thus rule out a sympathetic over-activity secondary to the lowered arterial blood pressure as the mechanism of action of PGE1. A possible direct interference with the adrenergic receptor system of the pancreatic islets was also ruled out since the inhibitory effect of PGE1 was not overcome by phentolamine pre-treatment.