Anti-anaphylactic effect of sinomenine was studied in guinea-pigs sensitized with bovine serum. Fairly constant severity of shock was obtained in the control animals by determining challenging dose based on Prof. Ogata's so-called binding zone: the highest mutiplication of the antigen giving positive reaction with the highest dilution of the antibody. Standard dose for challenge was calculated by the formula. body weight (g)×1/13×1/binding zone. Sinomenine was effective in preventing the guinea-pig's anaphylactic shock, but not so remarkably. Five daily subcutaneous injections of 50mg/kg sinomenine were required to prevent death from the active anaphylactic shock induced by the standard antigen dose. Under this pretreatment only about half number of the animals have survived death from the passive anaphylaxis shocked by the same antigen dose. Therefore, sinomenine seemed to be less effective in preventing guinea-pig anaphylaxis than canine anaphylaxis, against which marked protection was observed by one of us (R. N.) In the guinea-pig injected sinomenine 50mg/kg for 5 consecutive days, histamine content of skin of the head region was reduced by ca. 26%, but no reduction was observed in the abdominal skin and lung tissues. This degree of histamine release was much less than in the dog. The guinea-pig became more susceptible to histamine after the repeated injection of sinomenine, but this phenomenon is not specific to this species. Sinomenine did not inhibit the precipitin reaction in the guinea-pig anaphylaxis. From these, it may be concluded that the protective effect of sinomenine against guinea-pig anaphylaxis is less marked than against canine anaphylaxis and this is chiefly due to lesser ability of sinomenine in releasing histamine in this species.