Insulin and insulin-like growth factor I are known to be mitogenic and therefore may play a role in the development of endometrial cancer. We undertook this study to investigate whether human endometrial cancer tissue has receptors for these substances. Endometrial cancer tissue samples were obtained at hysterectomy from 10 women with endometrial cancer, and control endometrial tissue was collected from normal cycling women undergoing hysterectomy for nonendocrine problems. Binding studies with iodine 125-insulin and [125I]insulin-like growth factor I revealed the presence of specific binding sites for insulin and insulin-like growth factor I in both normal endometrium and endometrial cancer tissue. The percent binding of [125I]insulin in the endometrial cancer tissue (mean +/- SE 2.4% +/- 0.5%/100 micrograms protein) was not significantly different from that in normal endometrium (3.5% +/- 1%/100 micrograms protein). On the contrary, the percent total binding of [125]insulin-like growth factor I in the endometrial cancer (5.3% +/- 1.5%/100 micrograms protein) was significantly (p less than 0.04) higher than that observed in normal endometrium (2.1% +/- 0.4%/100 micrograms protein). There was a significant positive correlation between the histologic grade of the tumor and the insulin-like growth factor I binding (r = 0.865, p less than 0.02). The affinity constants for the high-affinity receptors were similar in the normal and neoplastic endometrium. These results indicate that insulin and insulin-like growth factor I may play a role in the growth and development of endometrial cancer.