These experiments were carried out to study the influence of prostaglandin A1 (PGA1) on basal and glucose—stimulated insulin secretion in anesthetized dogs. During intravenous PGA1 infusion (0.25 μg/kg/ min), no changes in basal insulin levels occurred, in spite of the significant increase in plasma glucose and free fatty acids (FFA). Following iv glucose tolerance test (0.33 gAg), PGA1 treated dogs exhibited significantly higher plasma glucose and FFA levels and lower mean glucose disappearance rate than controls. An impaired insulin response to glucose loading was observed in dogs receiving PGA1 as shown by the plasma insulin concentrations and by the mean integrated insulin areas and insulinogenic index. The PGA1 infusion rate did not cause any modifications of the blood flow in splanchnic area, while it significantly reduced the systemic arterial pressure. These findings allow us to exclude that a modified pancreatic perfusion may be responsible for the inhibition of insulin secretory response.(Endocrinology92: 6, 1973)