Dichloromethotrexate (DCM), a dihalogenated analog of methotrexate (MTX), is a potent classic folate antagonist that is metabolized and excreted by the liver. It is not nephrotoxic nor are its pharmacokinetics significantly affected by changes in renal function. Therefore, the feasibility of administering a maximum tolerated dose of DCM in combination with high-dose ciplatin (CDDP) was investigated in patients with head and neck, bladder, or cervical cancer--three epithelial carcinomas known to be responsive to single-agent CDDP and MTX. The overall response rates in 24 evaluable patients with head and neck cancer, 21 evaluable patients with bladder cancer, and 22 evaluable patients with cervical cancer were 54%, 57%, and 50%, respectively. Complete response rates of 25%, 19%, and 36%, respectively, were observed. DCM can be administered on a weekly schedule at a maximum tolerated dose in combination with CDDP with tolerable side effects and without significant nephrotoxicity.