Sinomenine is an alkaloid contained in the root of Sinomenium acutum Rehd. et Wilson (Fam. Menishermaceae), growing wild in southern Japan, and has long been used as a home remedy for neuralgia and rheumatism. It has a chemical structure similar to that of morphine, as shown left (1). Ishiwari (2, 3), who first isolated this alkaloid and studied its pharmacological actions, found that sinomenine caused depression of blood pressure by dilating peripheral blood vessels in mammals and acceleration of thoracic lymph flow in dogs. He (4) assumed that the foregoing therapeutic effect of this alkaloid was probably due to the increased circulation in the locus by such peripheral vascular effect.Augmentation of lymph rich in protein caused by sinomenine (5) is also observed in the case of histamine(6), as well as with peptone (7, 8) and anaphylaxis (9) where histamine liberation is known to occur. Depression of arterial pressure by sinomenine is generally accompanied by the increase of portal pressure and liver volume (5), which phenomena are also known with peptone and in anaphylaxis (10). Recently, MacIntosh and Paton (11) observed that a marked liver congestion was caused by some organic bases which liberate histamine. The known side-effects of sinomenine are erythema, urticaria, pruritus, and facial swelling (4, 12).In the previous report (13), the author found that the lymphagogic and liver congestive actions of this alkaloid, and the wheal caused by its intradermal injection are notably reduced by the pretreatment or combination with Benadryl.The present series of experiments were undertaken in order to solve the problem of whether the afore-mentioned effect of sinomenine observed in dogs were the result of liberation of histamine.