The present studies were designed to determine the fetal catecholamine and metabolic responses to insulin-induced maternal hypoglycemia. Maternal hypoglycemia was induced by a primed constant infusion of insulin and glucose administered to pregnant ewes to maintain maternal glucose at 20-25 mg/dl. Maternal and fetal samples for measurement of catecholamine, glucose, and free fatty acid levels and arterial blood gas analysis were collected before insulin infusion and at intervals thereafter for 6 h. Maternal and fetal plasma catecholamine levels increased significantly in response to hypoglycemia (analysis of variance, P less than 0.01). Fetal insulin and glucagon levels did not change despite a 50% reduction in fetal whole blood glucose concentration. Fetal free fatty acid levels increased significantly during hypoglycemia (P less than 0.05). There were no significant changes in maternal or fetal heart rate, blood pressure, or arterial blood gases during hypoglycemia. These results suggest that the fetus is capable of responding to hypoglycemia with an increase in catecholamine and free fatty acid levels. These results are consistent with the interpretation that the fetus is able to mobilize alternative energy substrates in response to maternal insulin-induced hypoglycemia.