Experiment was carried out to see the changes in anaphylactic reactions and in the release of histamine from the liver and skin in the dogs of which histamine was previously depleted by a histamine liberator, sinomenine; and in addition, the effects of combined use of sinomenine and antihistamines were studied. In the sensitized dogs receiving a single intravenous injection of 3 mg/kg sinomenine or repeated injections of the same dose for 5 days, general symptoms of anaphylaxis were evidently milder than those in untreated control; and the maximum fall of blood pressure in 11 dogs was 4-58 per cent (average 24.4 per cent), whereas it was 80-100 per cent (average 88.8 per cent) in 23 dogs of untreated controls. In these sinomenine-treated dogs the increase in flow of the thoracic lymph and the rise of protein content of the lymph in anaphylaxis were lesser and the duration of incoagulation of lymph was shorter than in the case of the control. In the dogs given repeated subcutaneous injections of sinomeine the histamine release from the liver and skin in anaphylaxis was clearly less than that in untreated controls. Approximately the same results were obtained in the case of combined use of sinomenine with 3 mg/kg of Benadryl or Neoantergan. The precipitin reaction in sensitized dogs was not interfered by pretreatment with sinomenine. From these results it was concluded that the release of tissue histamine is largely responsible for anaphylactic reactions in dogs.