It was recently speculated that leptin may exert a direct inhibitory effect upon insulin release from the pancreatic B-cell. This proposal meets, however, with two objections. First, although the message for leptin receptors is indeed detected in rat pancreatic islets, the short form of this receptor, for which no signalling function is known, represents the major species present in islet cells. Second, in the isolated perfused rat pancreas, leptin (1.0 nM) fails to affect the release of either insulin or glucagon.