A prospective clinical trial using combination chemotherapy consisting of cyclophosphamide, doxorubicin, cis-Platinum and megestrol acetate (CAP-M) was initiated to study its effect on advanced or recurrent endometrial adenocarcinoma. Fifteen patients were clinically evaluable. Nine patients (60%) demonstrated an overall objective clinical response resulting in either complete regression of disease (33%) or a reduction in tumor size. For all responders the mean progression free interval was eight months, with a range of five to 11 months. Similarly, a mean survival time of 12 months with a range of five to 21 months was observed. An additional four patients showed no progressive disease for a mean of seven months duration. Reversible cis-Platinum-induced nephrotoxicity occurred in two patients. This is the first reported series of endometrial cancer patients using nonhormonal cytotoxic agents, including cis-Platinum, in conjunction with a progestin. This preliminary experience is encouraging and appears worthy of further clinical evaluation.