Prostacyclin /PGI2/ administered intra-arterially or intravenously to patients with peripheral vascular disease exerted a hyperglycemic effect. In normoglycemic patients receiving PGI2 at a dose of 5 ng/kg/min these effects were barely detectable, but they became unmasked by a rapid glucose injection. In diabetic patients the same PGI1 dose led to distinct elevation in blood glucose. Prostacyclin at a dose of 10 ng/kg/min raised blood glucose levels both at rest and after stimulation with glucose, and opposed effectively hypoglycemic action of tolbutamide in non-diabetic patients. PGI2 repressed glucose-induced insulin release in some normoglycemic patients but in others it either increased it or did not affect it. While hyperglycemic effects are reversible when PGI2 infusion is stopped, and do not interfere with the usual therapeutic administration of prostacyclin for a few days they, nevertheless, might constitute a risk in a patient with poorly controlled diabetes.