It is known that insulin release is calcium-dependent and that calcium-antagonists, blocking calcium transport across cell membranes, inhibit it, especially interfering with the second phase of insulin secretion. Gallopamil (GAL) is a new calcium-antagonist that, although structurally similar to verapamil, has more potency. It blocks slow calcium channels and fast sodium channels. Even if it has been demonstrated in vitro, there is no evidence that GAL is able to impair the glucose-induced insulin release in humans. We have submitted five normal subjects (24-36 yr old) to oral glucose tolerance test (OGTT, 75 g of glucose p.o.) and OGTT plus GAL infusion test (1 mg i.v. as a bolus, followed by a 2 mg/hr infusion for 2.5 hr, starting 30 min before glucose load), in two different days, to determine the effects of GAL on insulin and C peptide release after oral glucose load. In opposite with verapamil effects, we found that GAL did not reduce the peak levels of insulin and C peptide, but the peak response was delayed and the incremental areas tended to increase during GAL infusion, so that an impairment of glucose tolerance was equally obtained. This study indicates that different calcium-antagonist drugs exert differential effects on insulin release and their action on glucose homeostasis should be kept in mind because of the large use of these drugs in cardiac patients.