A B S T R A C T We studied the role of the direction of intrahepatic blood flow upon the location of hepatocyte formation in regenerating liver. Single liver lobes in the dog were autotransplanted to the region of the neck with the blood supply reestablished in a manner to perfuse the hepatic lobule from portal tract to central vein or, in a reverse direction, from central vein to portal tract. Partial resection of the nontransplanted liver was later performed to induce regeneration in the grafts by humoral means. Tritiated thymidine was administered, and radioautographs were prepared from excised graft and nontransplanted liver. In the "straight" blood flow grafts, as well as in all nontransplanted livers, labeled hepatocytes indicating DNA synthesis were found predominantly in the vicinity of the portal tracts. In the "reverse" blood flow grafts, labeled hepatocytes were more prevalent about the central veins. Thus, the localization of hepatocyte formation in the lobule during active liver regeneration cannot be attributed to an inherently greater capacity of periportal liver cells to divide but is probably related to their preferential exposure to blood constituent changes (humoral mechanisms). Hepatocyte regeneration in the presence of abnormal directional circulation might lead to lobular disorganization resulting in consequent biochemical aberrations despite the formation of new cells.

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