The addition of insulin or insulin-like growth factor I (IGF-I) to RIE-1 cells increased the expression of the primary response gene cMG1; dose-response analysis suggested that this effect was mediated largely through type 1 IGF receptors. Insulin/IGF-I did not affect the expression of the cMG1-related genes TIS11 and TIS11d, whereas epidermal growth factor, angiotensin II or 12-O-tetradecanoyl phorbol-13-acetate stimulated the expression of all three genes. Incubation with wortmannin (WM) prevented the insulin/IGF-I-induced elevation of cMG1 mRNA, but not that induced by the other mitogens or the stimulation of mitogen-activated protein kinase by insulin. We conclude that WM-sensitive phosphatidylinositol 3-kinase may be involved in the specific stimulation of cMG1 expression by insulin/IGF-I.