1. The histamine content of the skin has been determined in untreated cats, in cats injected with the histamine liberator, compound 48/80, and in cats injected subcutaneously with an oily suspension of histamine or histidine after treatment with compound 48/80.2. Skin histamine in cats varied from 2.2 to 37.5 mug/g. Apart from regional variations in the histamine content of the abdominal skin, lower values were obtained from cats kept on a laboratory diet which included aureomycin (mean 8.5 mug/g, range 2.2-13.1) than from cats on a high protein diet without aureomycin (mean 17.5 mug/g, range 5.2-37.5).3. Compound 48/80 caused a depletion of skin histamine which was never complete, and a residue of 3-7% remained; in cats which originally had a low histamine content of skin, depletion was even less and up to 20% of the original histamine remained.4. Recovery of skin histamine in cats after injections of compound 48/80 was slow, at least 110 days being required for full restoration. The rate of recovery was not altered by daily subcutaneous injections of histidine, but an effect was found with daily subcutaneous injections of histamine. Histamine had no effect for the first 33 days, but at 55 days the percentage histamine content of the skin was greater than in the cats treated with histidine or the oily suspending vehicle, and at 110 days the histamine content was not only much greater than the other two groups but was greater than that before injection of compound 48/80.5. No in vitro histamine formation was detected in the skin samples either before compound 48/80 treatment or at any time during the subsequent recovery of the histamine to control levels.6. The results support the theory that the histamine found in skin tissues of the cat is not formed there but is taken up from the blood stream.