Post-hepatic insulin secretion was measured in six chronically catheterized fetal lambs (fetal weight 2.8 +/- 0.3 kg, mean +/- S.E.M.) and the results were compared with those obtained in nine prematurely delivered newborn lambs (birth weight 3.1 +/- 0.3 kg and postnatal age 1.3 +/- 0.2 days). The fetal and neonatal lambs received either a 0.45% saline or a glucose infusion respectively, which resulted in a 2-fold increase in the plasma glucose concentration. [131I]insulin was infused for 110 min to determine the rate of insulin secretion during a steady state of plasma glucose concentration. Post-hepatic insulin secretion and the metabolic clearance rate were calculated. With the 2-fold rise in plasma glucose concentration, the post-hepatic insulin secretion rate increased significantly in the newborn lamb and in three out of four fetuses. The plasma insulin concentration increased significantly in the fetus (11 +/- 4.0 to 35 +/- 8 microU/ml, P less than 0.05) during glucose stimulation as a result of decreased metabolic clearance rate of insulin (10.6 +/- 1.9 to 6.3 +/- 1.8 ml . kg-1 . min-1) and an increase in post-hepatic insulin secretion rate. In spite of an increase in post-hepatic insulin secretion rate, the increase in plasma insulin concentration in the newborn lamb was not significant because of large variation in the values obtained. The data suggest that pancreatic beta-cells in the newborn and in the fetal lamb are equally responsive to a 2-fold increase in plasma glucose concentration.