To evaluate the role of hexamethylmelamine (HMM) in the treatment of endometrial cancer, 20 women with metastatic or recurrent endometrial carcinoma received HMM orally at a dose of 8 mg/kg/day. Six patients (30%) showed a partial response, with a median duration of response of 3.5 months and a range of 1 to 7 months. Two patients responded to HMM as a second-line agent following previous treatment with nonhormonal chemotherapy. There were no complete responses. The major toxicities noted with HMM therapy were nausea, vomiting, and neurotoxicity. In 6 patients (30%), therapy with HMM was discontinued because of toxicity. Although HMM is active against endometrial cancer when given at a dose of 8 mg/ kg/day, it appears to have limited usefulness because toxicity precludes its prolonged administration.