Based on the in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (cisplatin), we designed a phase II trial of Ara-C with cisplatin for patients with colorectal adenocarcinoma. Forty-eight eligible patients received continuous infusion Ara-C, 30 mg/m2/day over 72 hr, plus cisplatin, 30 mg/m2 for three doses at hours 12, 36, and 60 of the Ara-C infusion. The objective partial response rate for patients with colon carcinoma was 3% (1/32 patients; 95% CI, 0-16%) with a median response duration of 2.8 months. None of the 16 patients treated for rectal carcinoma responded. Myelosuppression was the most severe toxicity. Significant gastrointestinal and hepatic toxicities occurred in a small number of patients. Nephrotoxicity and neurotoxicity were mild. We conclude that the prolonged infusion of Ara-C in combination with divided doses of cisplatin offers no significant therapeutic advantage.