Islet-activating protein (IAP) is one of the pertussis toxins. The ability of IAP to cause potentiation of insulin secretory responses and promotion of leukocytosis was studied in six animal species (hamsters, rats, guinea pigs, rabbits, dogs and monkeys). The action of IAP on insulin secretion in the animals was estimated by three kinds of tests: effects on epinephrine hyperglycemia, plasma insulin and blood glucose concentrations following the injection of stimuli, and glucose tolerance. Of all animals tested, IAP was most effective in hamsters. Marked hyperinsulinemia was also shown in IAP-treated dogs, rats and monkeys in response to insulin secretagogues, but their sensitivity to IAP was inferior to that of hamsters. In rabbits, IAP was markedly toxic, and the effect on insulin secretion was observed only slightly at a dose close to its minimal lethal dose. In addition, no significant effects of IAP were shown in guinea pigs in the present experiment. On the other hand, leukocytosis promoting activity of IAP appeared in a dose dependent manner in all animal species; rabbits were the most sensitive to IAP in this regard. It is concluded that both actions of IAP appear differently in different animal species, and the species difference of the effect on insulin secretory responses is in agreement with that on histamine sensitizing activity.