In a total of 113 cases of endometrial neoplasm, we studied the immunohistochemical expression of estradiol (E2), epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and epidermal growth factor receptor (EGFR). Positive immunoreactivity of E2 was found in 61% of the neoplasms. E2 immunoreactivity correlated well with high histologic grade and early clinical stage. Positive immunoreactivity for EGF or EGFR was found in 25.6% or 53.1% of the neoplasms, respectively. However, this was unrelated to histologic grade or clinical stage. On the other hand, TGFalpha immunoreactivity was found in 67% of endometrial neoplasias and was correlated with poor histologic grade and advanced stage. Contingency tables indicated a significant negative association between the status of E2 and that of TGFalpha. Simultaneous expression of E2, EGF and EGFR, or E2, TGFalpha and EGFR was found in 6.8% and 15.9% of endometrial carcinomas, respectively. These results suggest that a predominant number of endometrial carcinomas escape autocrine/paracrine growth regulation by EGF and E2 or TGFalpha and E2, and that TGFalpha may be involved in the progression of endometrial carcinoma.