Male Wistar rats were received daily i. m. injection of hydrocortisone 10 mg/kg for 28 days. The histamine contents in the inner and outer layers of the skin, the majority of skin mast cells being contained in the former, began to decrease after 14 days, and in the jejunum decreased after 7 days, while there was an increase in histamine in the pyloric stomach after 7 days. In the control group receiving normal saline, no significant change was observed in these tissues during 28 days of injection except a slight increase in the pyloric stomach. The i. p. injection of sinomenine 50 mg/kg caused a marked (43%) reduction of histamine content in the inner layer of skin which completed within 60 minutes. In other tissues, the pyloric stomach and jejunum showed only a slight and transient reduction recovering before 24 hours. A single injection of hydrocortisone 10 mg/kg inhibited the histamine reduction by sinomenine in the inner layer of skin. But after repeated injection of hydrocortisone over 14 days such inhibition could no longer be observed on the histamine release due to sinomenine. In the adrenalectomized rats, the histamine contents of all these tissues were increased, most remarkable increase being in the pyloric stomach. There was no reduction of histamine in the skin after the injection of sinomenine despite appearance of a marked edema in the snout and pads.