Controversy over the chemotherapy of uterine cancers still exists. This study was designed to directly compare the efficacy of various chemotherapy combinations, CAP (Cytoxan, Adriamycin, cisplatin), CAF (Cytoxan, Adriamycin, 5-fluorouracil), MF (melphalan, 5-fluorouracil), CP (Cytoxan, cisplatin), to single agents, Adriamycin (DXR), Cytoxan (CYT), cisplatin (DDP), and carboplatin (CARBO). Five human endometrial cell lines and one sarcoma cell line were used: AE7, ECC-1, HEC1A, HEC1B, AN3, and SKUT1B. The ATP chemosensitivity assay was used to determine dose-response curves of various treatments. By using mean IC50's for comparison, CAF and MF were twice as effective in cell kill as CAP (P = 0.01, 0.03, respectively). There was however no significant difference between CAF, MF, and DXR (P = 0.12, 0.46, 0.34). When dose comparison is used, combinations CAP, CAF, and MF appeared to be 3 to 15 times more potent than DDP, CYT, or CARBO. In summary, Adriamycin remained the most effective single drug for uterine cancer cell lines. Its cytotoxicity was equivalent to that of combinations CAP, CAF, and MF.