Cysteine-rich intestinal protein (CRIP) has been implicated as an important zinc-binding protein in the rat intestine. However, its specific role remains undefined. As an approach to the ultimate elucidation of the function of CRIP, we have explored the role of glucocorticoids and L-thyroxine (T4) in the increase of CRIP mRNA that occurs during postnatal development. Hydrocortisone administration on day 10 elicited a precocious increase of CRIP mRNA. The response to hydrocortisone was readily detectable 12 h after injection. Lack of endogenous glucocorticoids in rat pups adrenalectomized on day 9 impeded but did not prevent the normal rise of CRIP mRNA. Furthermore, injections of dexamethasone (DEX) on days 10, 16, and 18 led to a loss of responsiveness of CRIP mRNA as the pups matured. The administration of T4alone resulted in a small increase of CRIP mRNA, whereas when combined, T4and DEX synergis-tically raised the concentration of CRIP mRNA. All of these patterns of response to hormone manipulation indicate the possibility that CRIP is a mediator of glucocorticoid action on the developing intestine. They do not appear to support the hypothesis that CRIP plays a role in zinc transport during the postnatal period. The potent effects of glucocorticoids and T4on CRIP mRNA levels should provide useful tools for further investigations in this area.