The adrenal glands were excised from anesthetized dogs and sliced with a razor blade. In each slice the medulla was removed and was minced. Aftre trypsin digestion, the dispersed cells were collected and preincubated in medium containing lima bean trypsin inhibitor. The incubation was carried out both with or without test drugs for 2hr, and thereafter cortisol released into the medium was determined. When histamine (Hi) was added to dispersed cells, cortisol was released in a concentration-dependent fashion. A significant release was noted at concentrations higher than 10-(8)M of Hi. When various concentrations of ACTH and db-cAMP were added to dispersed cells, both brugs exhibited dose-dependent corticosteroidogenesis (CSG). Hi-induced CSG was inhibited by pretreatment with Ca-blockers and pyrilamine, but not affected by pretreatment with phosphobiesterase inhibitors and cimetidine. These findings indicate that Hi-induced CSG is related to H(1) receptors and Ca(2+) influx but not with cAMP and H(2) receptors.