Purpose We have previously demonstrated that 2-methoxyestradiol (2-ME) inhibits the growth of human endometrial cancer HEC-1-A and RL-95-2 cells in vitro. In this study, we examined the effects of 2-ME on human endometrial carcinoma in severe combined immune deficient (SCID) mice. The potential side effects of 2-ME on SCID mice were also investigated. Methods Severe combined immune deficient mice were injected with HEC-1-A cells (1 X 10(6)/mouse) and a 18 day administration of 2-ME was followed after 1 week cell implantation. Tumor volume, weight, body weight and blood chemistry were determined. Tumor tissues were examined with an antibody against the proliferative cell nuclear antigen (PCNA) and Ki-67. Liver, spleen, kidney, heart, lung and uterus were screened by pathological examinations. Results 2-ME (100 mg/kg p.o.) did not inhibit the growth of human endometrial carcinoma as compared to control. Necrotic areas were similar in both 2-ME-treated and -untreated tumor tissues. The expressions of PCNA and Ki-67 were similar in 2-ME-treated and untreated tumor sections. The wet weight of uterus was increased to more than threefold. The epithelial cells and glands in endometrium were increased. No significant difference was detected in blood AST, ALT and BUN. Conclusions 2-ME has no antitumor effects on human endometrial carcinoma in our animal model. Its proliferative effects on endometrium and uterus might limit its use in gynecological cancers.