The effects of neonatal androgenization on endometrial carcinogenesis and natural killer (NK) cell activity which may facilitate the development of malignant tumors were studied. Abnormal uterine proliferation was not detected in any of 162 NR during a 800-day observation period. In contrast, 3 atypical hyperplasias, 3 adenocarcinomas and one squamous cell carcinoma of the uterus were detected in 61 ASR after 500 days of age. In ASR, obesity became prominent with aging and spleen weight also increased after 500 days of age. Concerning the target cell of NK cell activity assay, YAC-1 lymphoma cells are the best cell line of the three cell lines in a variety of experimental conditions. NK cell activity of both NR and ASR decreased with age. NK cell activities of ASR significantly decreased at both 250 and 500 days of age in comparison with those of NR. Such persistently reduced NK cell activity which implies that a decline in immune surveillance is one of the important factors in endometrial carcinogenesis of ASR after 500 days of age.