Histamine metabolism of a transplantable syngeneic spontaneous murine mammary adenocarcinoma with a high degree of undifferentiation was studied. The endogenous histamine content is significantly higher than in normal intestine and lung. This is not due to an increase of the histamine biosynthetic capacity, which is lower than in the lung. The administration of histamine, 0.1 mg per kg body, for 7 days, decreased significantly the biosynthesis of histamine in the tumor, but not its endogenous histamine content; in the intestine and in the lung no significant modification of histamine biosynthesis was observed. It has also be shown that the proportion of radioactivity in the purified nuclear fraction of the tumor is significantly higher than in the intestine, after incubating either tissue with 3H-histamine. Since the mast-cell content of the tumor has been found to be low, our results should be considered as a specific alteration of the function of histamine in these tumor cells.