After injecting intravenously an appropriate dose of the antigen serum calculated from the binding zone and the blood volume by Ogata's antibody dilution method to 23 dogs sensitized with bovine serum, it was possible to bring about the maximum fall of blood pressure well over 80 per cent (average, 88.8 per cent) within 30 minutes. In the case of other 21 sensitized dogs given intravenous injection of 10 mg/kg Benadryl 30 minutes prior to the reinjection, the maximum fall of blood pressure in 1-79 per cent (average, 43 per cent) was elicited after injecting the same dose of the antigen; and in a few instances the fall of blood pressure was practically protected. Such a suppressive effect of Benadryl was evidently more marked than the effect on the blood pressure fall induced by histamine. In Benadryl-treated dogs, a rise of the portal pressure in anaphylaxis was slower and milder although the inhibition of the elevation by histamine was more complete. Benadryl in anaphylaxis showed a more incomplete inhibition on the acceleration of the lymph flow from the thoracic duct and on the increase in protein of the lymph than that on the similar changes induced by histamine. The duration of incoagulation of the lymph in anaphylaxis was shortened in Benadryl-treated dogs. When Benadryl was added to antibody serum in vitro or in vivo (by intravenous injection), the precipitin reaction (by the method of diluting antibody) was suppressed. In the case of sensitized dogs previously injected with Benadryl, after antigen reinjection a considerable amount of antibody (precipitin) not consumed in reaction remained in circulating blood, gradually decreasing up to 48 hours later; whereas in unprotected dogs precipitin was found to have disappeared promptly after the reinjection. These findings indicate that Benadryl inhibits the union of antigen and antibody through some reversible means. Consequently, it appears that this anti-anaphylactic effect of Benadryl observed in dogs is caused not solely by the counteraction against histamine being released. The fact that Benadryl has only shown a much weaker inhibition on the congestion of the liver as reflected by the increase in portal pressure and thoracic lymph flow than that on the fall of arterial pressure suggests that the sluice reaction of hepatic vein is caused by "intrinsic histamine" released and/or some smooth muscle stimulating factors other than histamine.