Preclinical and clinical studies have been performed to evaluate the efficacy of gemcitabine (2',2'-difluorodeoxycytidine; dFdC) in human renal cell carcinoma. Experimental data corroborated dFdC as an effective drug against cell lines from renal cell carcinomas (ACHN, A-498, SN12C) at concentrations much below clinically achievable doses. ACHN-bearing nude mice showed an overall response rate of 27% to dFdC (3 mice with complete response, 1 with partial response, 3 with stable and 8 with progressive disease). Objective response from 37 evaluable patients was 8.1% (1 patient with complete response and 2 patients with partial response). Gemcitabine was well tolerated thus, although gemcitabine at the dosage and schedule chosen had only small activity, the observed toxicity may permit further dose escalation or a more frequent administration of the drug.