Tissue specimens were excised from the liver, spleen, and from the skin of back and lips of dogs before and after intravenous injection of Witte peptone, sinomenine, polyvinyl pyrrolidone (PVP) and corbicula extract, and the mast cells of these tissues were examined for comparative study of the effect of these substances. The disruption of mast cells in the liver tissue was extremely marked after injection of pepton, but the change in the skin mast cells was only slight. In contrast to this, after the injection of sinomenine and PVP the disruption of skin mast cells was marked, but the change in the liver tissue was slight. Mast cells of the spleen were only slightly disrupted by any of these drugs. In the lip skin changes of mast cells by PVP and sinomenine were stronger in the superficial region rather than in the deeper tissue. In the liver and skin tissues it was confirmed that the degree of morphological change of the mast cells is parallel with the percentage rate of histamine release. Corbicula extract did not bring about any change of mast cells in any of these organs above mentioned. This substance simulate peptone in a lymphagogue action and in reducing coagulability of lymph, but does not release tissue histamine (Takaoka, 1957). These findings indicate that histamine released by these substances is derived from mast cells. The reason of occurrence of the tissue difference in the mast cells disruption by different substances was discussed.