A large body of evidence support the existence of an intratesticular Insulin-like Growth Factor I (IGF-I) system that can be viewed as a positive regulator of testicular functions. IGF-I may act at the testis level as a paracrine and autocrine differentiating factor. In the present study the role of IGF-I on Sertoli cell protein synthesis at transcriptional level has been investigated by evaluating the effect of IGF-I on nuclear RNA polymerase II activity as well as on total protein synthesis. Sertoli cells isolated from midpubertal rats and cultured in the presence of physiological doses of IGF-I showed a significant increase in nuclear RNA polymerase II activity (+80%) which appears to be correlated with a 50% increase in overall protein synthesis and a 40% increase in Androgen Binding Protein (ABP) production. These data provide the first evidence for a conceivable role of IGF-I in the modulation of Sertoli cell development through a direct action at the transcriptional level resulting in augmented protein synthesis.