Rats bearing Reuber H-35 or Novikoff hepatomas and mice bearing L1210 or L5178Y murine leukemias exhibited elevated serum levels of fetuin : N-acetylneuraminic acid transferase (EC 220.127.116.11) activity. The serum transferase activity could be correlated with the growth rate of the tumor; in animals bearing the more rapidly growing Novikoff hepatoma, activity was higher than in animals bearing the Reuber H-35 hepatoma. Higher transferase levels were also found in L1210 leukemic mice than in mice with the slightly slower growing L5178Y leukemia. Serum from rats bearing Reuber H-35 hepatoma and mice bearing L1210 murine leukemia had elevated levels of alpha- and beta-glucosidase (EC 18.104.22.168 and EC 22.214.171.124), alpha- and beta-galactosidase (EC 126.96.36.199 and (188.8.131.52), beta mannosidase (EC 184.108.40.206), alpha- and beta-fucosidase (EC 3.2.1.- and EC 220.127.116.11), beta-N-acetylglucosaminidase (EC 18.104.22.168) and acid phosphatase (EC 22.214.171.124); alpha-mannosidase (EC 126.96.36.199), beta-N-acetylgalactosaminidase (EC 3.2.2.-) and beta-xylosidase (EC 188.8.131.52) were not elevated. In animals bearing Reuber H-35 hepatoma, host liver levels of glycosidases, beta-glucuronidase (EC 184.108.40.206) and acid phosphatase were elevated over both the control and the hepatoma values. The data are interpreted to mean that the tumors or various host tissues release large quantities of enzymes into the serum and that enzyme levels in host organs may also be affected by the tumor.