The influence of sialidase and sialyltransferase on the binding of 3H-estradiol to estrogen receptors in baboon uterus was investigated to ascertain if sialylation was involved. Specific binding capacity increased approximately 37% in the presence of sialidase, although Kd values essentially remained unchanged. 3H-Estradiol binding was correlated with free sialic acid in the presence of either sialidase or sialyltransferase. As sialidase concentrations were increased, 3H-estradiol binding and free sialic acid concentration increased linearly (r = 0.937, p less than 0.001). Incubation of 22 x 10(-5) U sialidase with its inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, decreased binding capacity and sialic acid concentration (r = 0.929, p less than 0.001). Although a decrease in binding capacity and free sialic acid concentration was observed in the presence of increasing amounts of sialyltransferase, a positive correlation was found between these two parameters (r = 0.839, p less than 0.035). A negative trend that was statistically insignificant was observed between binding capacity and sialic acid concentration when 2 x 10(-4) U sialyltransferase was incubated with the inhibitor, acetylsalicylic acid (r = -0.571, p = 0.195). The sialic acid concentration increased, while the 3H-estradiol binding capacity decreased. Collectively, these results show that both sialidase and sialyltransferase affect the binding of estradiol to its receptor in opposite directions. We suggest that biological activities of estrogen receptors in target cells may be regulated by the extent of sialylation of the receptor molecule itself. This posttranslational alteration may represent a new type of control mechanism for estrogen action.