Plasma and thoracic lymph were collected at definite intervals from dogs anesthetized with chloralose-urethane, their histaminase activities were measured by the Kapeller-Adler method modified by the present author, and the effects of histamine and histamine liberators, sinomenine and peptone, on such activities were examined. The effects so obtained were studied in relation to the changes in the histamine equivalent (Code's method) and in the protein concentration (refractometry) of the plasma and lymph. The histaminase activity of the thoracic lymph of normal anesthetized dog was 1.5-2.5 P.U. and this was slightly higher than that of the plasma. Intravenous injection of histamine (0.5 mg/kg) effected a slight but, distinct increase of histaminase activities of the plasma and thoracic lymph, and such changes were accompanied with the elevation of histamine equivalent. Sinomenine injection (3 mg/kg) also caused increases in the histaminase activities of both fluids with an attendant rise in histamine equivalent. In the case of peptone-Witte (150 mg/kg), the effect was different, from the foregoing two and, in spite of a marked increase in the histamine equivalent of the plasma and lymph, histaminase activity increased markedly only in the lymph and increase in the plasma histaminase was extremely slight. Intravenous injection of Benadryl (10 mg/kg) caused a transitory increase of, histamine equivalent in the plasma and slight elevations of histaminase activities were noticed in the plasma and lymph. Benadryl suppressed the lymph acceleration and the increase in plasma histaminase activity elicited by histamine injection. Changes in the histaminase activity were not essentially correlated to changes in the protein concentration. Consideration on the mechanism of extracellular liberation of the histaminase by these drugs leads to an assumption that a certain pharmacological action of histamine was partly responsible for the mechanism.