Carbamoyl-phosphate synthetase (ammonia) is homogeneously distributed in rat-liver parenchyma at birth, as demonstrated by immunohistochemistry. A heterogeneous distribution can first be demonstrated at 6 days post partum, but can be masked by use of a too sensitive detection system. This heterogeneity is established by a decrease in enzyme content around the hepatic venules and a considerable increase in enzyme content in the remaining parenchyma. The perivenous decrease in enzyme content does not occur in all hepatocytes synchronously. The adult type of heterogeneity is characterized by a perivenous layer, only two to three cells thick, in which carbamoyl-phosphate synthetase can no longer be detected, irrespective of the sensitivity of the assay used. This situation is fully established at the age of two months.