Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. The active protein possesses a molecular weight of 77, 000 and an isoelectric point of pH 7.8. The nature of IAP-action is characterized by enhancement of insulin secretory response to glucose and other stimulants. A single injection of IAP into spontaneous diabetes rats resulted in normalization of their glucose intolerance over a period of a month. Acute and chronic animal toxicity tests showed that LD₅₀ of IAP was 127 μg/kg in mice and 114 μg/kg in rats. After these animal experiments, phase 1 studies were designed and undertaken to establish dosage, duration of action and other factors. IAP of 0.5 μg/kg or 1.0 μg/kg did not bring about any serious toxic or adverse effects in five volunteers. On the 4th day of a single injection of IAP, insulin secretory response was proved to be enhanced. Follow-up studies showed that the IAP-action continued over a month or at most two months. Two features of IAP, i. e., the enhancement of insulin secretory response and the long duration of the action, were confirmed in healthy persons as well as in animals. As expected, IAP has a strong antigenic reaction resulting in formation of IgG antibody and possibly IgE antibody. The antigenicity of IAP causes some hindrance to clinical usefulness. For avoidance of anaphylactic reaction, IAP should be given repeatedly with care. The problem concerning antigen-antibody reaction should be overcome as soon as possible before the clinical use of IAP as a medicament.