The purpose of this study was to examine the relationship between natural killer cell activity and biological behavior of tumor, expressed by architectural (FIGO) and nuclear grading, depth of myometrial invasion, and proliferating cell nuclear antigen (PCNA) index in patients with endometrial carcinoma. Forty patients with FIGO stage I endometrial carcinoma, treated with radical surgery, were included in this retrospective study. At the time of diagnosis, natural killer cell activity of peripheral blood was evaluated against K562 target tumor cells and correlated with architectural and nuclear grading, depth of myometrial invasion, and PCNA index of the tumor. Natural killer activity diminished with increasing nuclear grade of the tumor ( P = 0.004); similarly, natural cytotoxicity decreased with myometrial invasion: for stages IC and IB endometrial carcinoma, the mean values of natural cytotoxicity were significantly lower than stage IA disease ( P = 0.0001). Natural killer activity was significantly correlated with PCNA immunostaining of the tumor ( r = -0.8). It is concluded that the natural immune reactivity seems to be related to the pathologic features of early stage endometrial carcinoma, showing a significant reduction in presence of nuclear pleomorphism and/or myometrial invasion, and also an inverse relationship with PCNA index.