Rats with transplantable spontaneously metastasizing mammary tumors have elevated levels of both serum sialoglycoconjugate and serum sialytransferase activity compared with normal female rats or rats with various nonmetastasizing mammary tumors. A direct relationship was observed between the amount of serum protein-bound sialic acid and serum sialyltransferase activity in all rats studied. Serum sialyltransferase activity in rats with a representative metastasizing mammary tumor, SMT-2A, was also correlated with tumor age. Microsomes prepared from the SMT-2A tumor have a sixfold higher sialyltransferase activity than do microsomes prepared from the nonmetastasizing mammary tumor MT-W9B. Normal rat liver microsomes have the same level of activity as microsomes prepared from livers of animals with either SMT-2A or MT-W9B tumors. The data indicate that spontaneously metastasizing mammary tumor cells have an increased production and release, perhaps through cell surface shedding, of a sialyltransferase. It is suggested that this sialyltransferase may increase the serum half-life of certain tumor-specific circulating glycoconjugates by increasing the content of protein-bound sialic acid and may thereby play a role in the immune escape mechanism of metastasizing tumor cells.