After intravenous injection of Prozime-10 (P-10) into anesthetized dogs, plasma cortisol rose slowly and reached a maximum 3.5hr or later. With an increase in the dose of P-10 to 10mg/kg, the maximum cortisol concentration increased dose-dependently. When DEP-treated P-10 was injected, a similar release of cortisol occurred but much less prominently than that induced by a corresponding dogs of non-treated P-10. When slices of the dog adrenal cortex were exposed to P-10, no significant release of cortisol was noticed, although ACTH released cortisol markedly. When P-10 was injected (i.v.), a transient but significant increase in plasma histamine (Hi) was noticed. When the sliced tissues were exposed to various concentrations of Hi, cortisol output increased along with an increase in Hi concentration. It became evident that the cortisol release from the sliced tissues due to Hi was provoked via H(1) receptors.