Three-week-old male rats were fed for two weeks diets supplying inadequate, adequate, or excess amounts of histidine. After the 2-week feeding of the experimental diets, the rats were killed. Brain, gastrocnemius muscle, kidney and stomach were removed and analyzed for histamine and free-histidine as well as for the degradative enzyme, HMT, and the histamine-synthesizing enzyme HDC. The following results were obtained: As the levels of dietary histidine increased, (1) tissue concentrations of free-histidine and of histamine increased in all the tissues analyzed. (2) The increase of histamine was greatest in brain and stomach (5- and 4-fold, respectively), but less in kidney and muscle (2-fold). (3) HDC activity was not detected in muscle, but doubled from the lowest to the highest histidine intake in brain and increased almost 6-fold between the lowest and the highest histidine levels in stomach. (4) Kidney HDC decreased from the lowest to the two higher levels of dietary histidine. (5) HMT activity increased nominally in brain and not significantly in kidney; none was detected in either muscle or stomach. (6) Brain and kidney, tissues with considerable HMT activity, had almost no histamine. The increases in tissue histamine concentrations observed in the tissues analyzed generally reflected the changes and magnitudes of enzyme activities for HMT and HDC. The results in the rat differ in important ways from those previously observed in chickens as follows: (1) Histamine concentrations as a function in dietary histidine decreased in the chick. (2) Both HDC and HMT activities were present in chick muscle tissue. (3) HDC activity in chick stomach decreased sharply as a function of dietary histidine.