Enzyme activity measurements of alkaline phosphatase in surgically removed human liver tumors showed elevated level of the enzyme in 6 focal nodular hyperplasias, reduction in 8 primary hepatocellular carcinomas, and no change in the 4 adenoma samples. The activity represented liver type of alkaline phosphatase nearly in all cases because it could be inhibited by L-homoarginine more extensively than by L- phenylalanine. Studies on polyacrylamide gel electrophoresis indicated the presence of a variant type isoenzyme only in one focal nodular hyperplasia and in two hepatocellular carcinomas, one of which showed a fibrolamellar structure whereas the other was associated to cirrhosis. The importance of the elevated amount of connective tissue in the tumor, resulting in an isoenzyme shift of alkaline phosphatase, received substantial support upon comparing chemically induced rat liver tumors with and without cirrhosis.