A quantitative assay of albumin messenger RNA (mRNA) in blood samples was designed using the competitive reverse-transcription polymerase chain reaction, and the significance of measuring albumin mRNA levels in the blood of patients with hepatocellular carcinoma (HCC) in hepatic resection was evaluated. Albumin mRNA levels were measured in the following: (1) peripheral blood in 11 patients with HCC and 20 control subjects without liver disease, (2) blood in the portal and hepatic veins in five patients with HCC immediately after laparotomy, and (3) a perioperative series of peripheral blood in eight patients with HCC. Two patients with HCC whose albumin mRNA level in peripheral blood was markedly high were both at stage IVa. On the other hand, 20 control subjects showed negative or F5 ุ 10 3 transcripts/g RNA of albumin mRNA expression. Immediately after laparotomy, the albumin mRNA levels in the tumor-draining hepatic vein were greater than in the portal and non-tumor-draining hepatic veins in four of five patients with HCC. Albumin mRNA levels in peripheral blood showed a marked increase after mobilization and/or resection of the liver and, thereafter, gradually decreased at postoperative day 7 in all eight patients with HCC. A new method to measure the albumin mRNA levels in blood samples was developed, and high albumin mRNA levels in the peripheral blood of patients with advanced-stage HCC suggest the presence of HCC cells in the circulation. Increased levels in the tumordraining hepatic vein could indicate the spontaneous release of tumor cells or nontumorous hepatocytes or an increased albumin transcription in activated blood mononuclear cells. An increase in the levels in peripheral blood during an operation is intermittent. Therefore, an increased albumin mRNA level in the tumor-draining vein suggests, but does not prove, that the increased albumin mRNA level reflects tumor cells entering the systemic circulation. This alone does not prove that the prognosis is worsened.