Analbuminemic rats differ from Sprague-Dawley rats (SD), their strain of origin, with respect to carcinogenic susceptibility of various organs. We compared hepatic changes after carcinogenic treatments in two kinds of analbuminemic rats with different genetic backgrounds (NAR isolated from outbred SD and F344-alb F344-congenk analbuminemic rats) as well as in their parent strains. After the rats were treated according to the Solt-Farber protocol [a single dose of diethylnitrosamine (DEN) followed by dietary 2-acetylamino-fluorene (2-AAF) plus partial hepatectomy], F344 and F344-alb demonstrated similar numbers of much larger hyperplastic hepatic nodules (HPN) than SD or NAR, while in the latter two cases, sizes are approximately the same, NAR had a greater number of HPN. When HPN cells of F344 rats were infused into the portal vein of F344 and F344-alb, followed by treatment with the Solt-Farber protocol, the transplanted cells formed almost the same numbers of colonies of almost equal size within the livers in these two strains of rats. With continuous administration of a 2-acetylamino-fluorene (2-AAF) diet, which can change the normally albumin-negative hepatocytes of analbuminemic rats to albumin-positive cells, this process occurred earlier in F344-alb than NAR, but almost the same numbers were reached after 30 days. The results demonstrate responses to significantly differ between NAR and F344-alb, with both resembling their parent strains to a large extent, indicating that genetic background has the major influence on susceptibility to hepatic carcinogenesis, rather than analbuminemia itself.