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The increase of a serum protein in the circulation of rats following partial hepatectomy or the injection of thyroid hormone (T3) is reported. This serum protein factor is present in normal rat serum and accounts for approximately 1% of the total serum protein. The protein disappears from the serum of animals bearing Morris hepatomas 7777 or 7800. The amount of serum protein factor diminishes as the tumors increase in size. The levels of this protein in the serum fall immediately following partial hepatectomy. At 24 hours following the operation, however, the levels are increased well over those found in normal rats. Increased levels persist for 12 days following partial hepatectomy. The serum protein is also increased following injections of T3 and is decreased in thyroidectomized animals. Elevated levels of T3 are correlated with elevated levels of the serum protein and both are correlated with increased hepatic DNA synthesis. Low levels of T3 are followed by low levels of serum protein resulting in a diminished capacity for hepatic DNA synthesis. Injection of purified serum factor into normal rats results in increased [3H]thymidine incorporation in liver cells. It is suggested that the synthesis of this serum protein is stimulated by T3 and DNA synthesis is influenced by the serum protein. The serum protein might be a humoral factor influencing metabolic events in hepatocytes or hepatomas or it might be a carrier for an agent that in turn has a direct effect on these tissues.

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