Summary1. The continuous infusion at sub-shock rates of histamine into the portal veins of dogs for periods exceeding 220 minutes results in the production of a definite liver lesion, distinguishable from the congestion observed after periods of histamine infusion less than 90 minutes, from the lesion of prolonged profound histamine shock, and from the cirrhosis of chronic histamine exposure. 2. The animals are not in shock and recover following discontinuance of the histamine infusion. 2. Liver lymph flow is greatly increased by histamine infusion, while brom-sulphthalein extraction is reduced only slightly. Circulatory conditions in the histamine treated liver have been discussed briefly in terms of these findings. 4. In a series of control animals receiving prolonged saline infusions into their portal veins definite histological changes were not observed in the liver.