This study, which was performed on rats, demonstrates that the changes in both mammary tissue and serum sialyltransferase activities parallel the growth of the mammary gland, as measured by the DNA content of the tissue. An increase in the specific activity of the enzyme was evident during rapid cellular proliferation, followed by a return to basal values upon cessation of growth and involution of the glands. This pattern occurred under 3 different experimental conditions: (a) pregnancy-lactation-weaning, (b) pseudopregnancy induced by stimulation of cervix, and (c) daily administration of 1 microgram estradiol and 3 mg progesterone to promote mammary development equivalent to that of late pregnancy and subsequent decay of mammary gland after withdrawal of hormonal treatment. Although it is difficult to differentiate whether the increase in tissue sialyltransferase is dependent on hormonal stimulation or as a consequence of growth, the elevation in serum sialyltransferase seems to be closely related to the degree of cellular proliferation.