The influence of portal blood factors on canine liver regeneration was studied with graded nonhepatic splanchnic evisceration, coupled with 44 and 72 per cent hepatectomies. In one type of experiment, the pancreas was retained while the rest of the intra-abdominal gastrointestinal tract was removed. In a second variety, total pancreatectomy was performed with preservation of the intra-abdominal organs. In a third kind of experiment, total nonhepatic splanchnic evisceration was performed. Liver regeneration after hepatectomy was decreased by all three kinds of viscera removed as judged by deoxyribonucleic acid synthesis, autoradiography and mitotic index. Pancreatectomy and nonpancreatic splanchnic evisceration caused almost equal decreases in the regenerative response. Total nonhepatic splanchnic evisceration essentially halted regeneration during the first three postoperative days and intraportal infusions of insulin or glucagon, or both together, did not reverse this effect. The decrease in liver membrane bound adenyl cyclase activity and biphasic change in liver cyclic 3', 5' -adenosine monophosphate concentrations normally seen after partial hepatectomy were disrupted after the various eviscerations. Adenyl cyclase activity and cyclic 3', 5' -adenosine monophosphate concentrations tended to be higher than normal in the eviscerated dogs. These observations provide more support for our previously proposed hypothesis that control of liver regeneration is by multiple factors. Pancreatic hormones are important modifiers of this response but, by no means, exercise exclusive control. Other substances of gastrointestinal origin, presumably including hormones and nutrient supply apparently play important specific roles. The volume of portal flow is a secondary and nonspecific, but possibly significant, factor.