The average histamine contents in different regions of the skin in the dog mentioned in the following are in the range of 8.4 to 42.4 μg/g. Of these regions the value is highest in the skin of the ear margin followed by the skin of pubic regions, anal margin, and areola of nipples, and the value decreases in the descending order of eyelids, bristle area, throat, vertex, lip, abdomen, back, thigh and metatarsus. As for the histamine content in the joint capsules, the average value for each of six joints, namely, the shoulder, cubital, arm, hip, knee and spring is in the range of 5-9 μg/g. The kind of joint has no bearing on the content of histamine. The histamine content in the joint capsules on the opposite sides, right and left, shows practically no difference. The intravenous or repeated subcutaneous administration of sinomenine, Compound 48/80, peptone or Irgapyrin evidently decreases histamine from all the regions of skin. The rate of the histamine depletion is in no way connected with the amount of skin histamine content. Although the degree of the depletion in the lip skin is relatively high, generally the rate of release does not vary by the difference in the region. The degree of histamine release from the joint capsule is far greater than in the case of the skin. Histamine is markedly decreased from the skin and joint capsules by the repetition of subcutaneous injection of Irgapyrin, but unlike other histamine releasers it does not at all reveal signs ascribable to the release of histamine. This phenomenon is probably related to anti-histaminic property of this compound. Such a histamine release can not be brought about by butazolidine alone. one of the components of Irgapyin. Concurrent use of antihistamines does not diminish the degree of the histamine release by the releasers but markedly lessens the symptoms caused by the latter. When sinomenine is injected intramuscularly it has hardly any effect on histamine release. The possible reason of genesis of and pathophysiologic significance about ununiformity of the histamine distribution in the skin are discussed.