Standardized rapid infusions of alanine were performed in six fetal lambs and three neonatal lambs to test the hypothesis that elevations of circulating amino acids may induce insulin secretion. Fetal insulin secretion was induced and exhibited a biphasic pattern with maximal elevation (61.8 +/- 18.5 microunits/ml) by 60 minutes of infusion. Alanine infusion was not associated with elevation of plasma glucose. Linear regression analysis delineated a significant relationship between steady state infusion concentrations of alanine and insulin (r = 0.70, p less than 0.01); the correlation was improved by adding glucose as an additional variable (r = 0.80). Alanine infusions into the neonatal lamb demonstrated a similar early pattern of secretion. Two combined glucose-alanine infusions were performed in two fetal lambs and demonstrated a significant effect on the timing of insulin release although no synergy could be demonstrated. Insulin secretion may be important in the modulation of fetal and neonatal amino acid utilization for fuel or protein accretion. Alanine-induced insulin secretion could have the effect of sparing alanine as a glucose precursor and would allow enhanced tissue uptake for transamination and protein synthesis.