We investigated the potential roles of insulin-like growth factor-I and epidermal growth factor, both multifunctional regulators of mammary physiology, in somatotropin-stimulated lactation of dairy cattle. One insulin-like growth factor-I mRNA (7.4 kb) was detected in lactating mammary tissue; however, it became undetectable after somatotropin administration. Four type I insulin-like growth factor receptor mRNA (11.3, 6.2, 4.9, and 3.3 kb) were detected in mammary tissue and primarily expressed in alveolar epithelial cells. All of these receptor mRNA markedly decreased in mammary tissue from somatotropin-treated animals, although the cellular distribution pattern of receptor gene expression did not change. One epidermal growth factor receptor mRNA (10.5 kb) was present in mammary tissue and predominantly expressed in alveolar epithelial cells. Epidermal growth factor receptor mRNA decreased after somatotropin administration. The results from this study are consistent with the idea that the stimulatory effect of somatotropin during lactation is in part due to its ability to regulate the expression of specific genes or the stability of their mRNA in mammary tissue. The data also suggest roles for insulin-like growth factor-I and epidermal growth factor, as well as their homologous receptors, in controlling cellular changes in the mammary gland during somatotropin-stimulated lactation.