Previous studies demonstrated that porcine galanin is a potent inhibitor of insulin secretion in many species but fails to alter human insulin secretion. To resolve whether this discrepancy was due to the use of a heterologous peptide or to a true species response difference, we studied the effect of a synthetic replicate of human galanin on glucose-stimulated insulin secretion in rats, dogs, and humans. On administration into rats, human and rat galanin significantly inhibited glucose-induced insulin responses to a similar degree. Similarly, porcine and human galanin significantly elevated canine plasma glucose and inhibited canine plasma insulin responses. In contrast, plasma glucose and insulin responses to glucose administration in humans were unaltered by the addition of human galanin at or above the maximum effective dose employed in dogs. Possible effects of galanin administration were seen on human glucagon and pancreatic polypeptide responses to glucose at the highest dose of human galanin infused. We conclude that galanin probably does not play a major role in modulating human beta-cell function.