Insulin-like growth factors (IGFs) and the type 1 IGF receptor (IGF-R) are involved in normal growth and development of the human prostate. Changes in levels of IGF-R and IGFs have been shown for several malignancies. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGF-R and IGF-II in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Messenger ribonucleic acid (mRNA) hybridization signals and immunoreactivity for IGF-R were localized primarily to epithelial cells, with less signal in stroma. IGF-R mRNA was significantly decreased by 42% in PIN and 35% in cancer cells compared to that in benign epithelium (P < 0.0001). IGF-R immunostaining was significantly decreased by 32% in PIN and by 42% in malignant epithelium compared to that in benign epithelium (P < 0.004). IGF-II mRNA was also localized primarily to epithelial cells. IGF-II mRNA was significantly increased by 30% in adenocarcinoma compared to that in benign epithelium (P < 0.03). Immunoreactivity for IGF-II was localized to both stroma and epithelium. Protein levels for IGF-II were not significantly increased in cancer cells compared to those in benign epithelium. The decrease in the type 1 IGF receptor and increase in IGF-II mRNA may affect prostate cancer proliferation and differentiation.