A total of 24 patients with advanced colorectal adenocarcinoma were entered into a phase I-II study of 5-fluorouracil (5-FU) and cisplatin, 21 of whom had previously received 5-FU. The starting dose of cisplatin was 20 mg/m2 diluted in 1000 cc normal saline, given over 20 h daily for 5 days, together with 600 mg/m2 5-FU diluted in 1000 cc fluid, given simultaneously over 20 h daily for 5 days. This regiment was given every 4 weeks. The dose-limiting toxicity was renal and cumulative. All 24 patients were evaluable for toxicity. Of 12 patients on the above-mentioned starting dose, 8 underwent a cisplatin dose reduction to 15 mg/m2 due to a progressive decrease in creatinine clearance following the second or third course of treatment. Of 12 patients who started cisplatin at 15 mg/m2 and 5-FU at 600 mg/m2, 11 were maintained at this dose. A WBC nadir count of less than 2000/mm3 was seen in four patients. Thrombocytopenia occurred in three patients who received 15 mg/m2 cisplatin and 600 mg/m2 5-FU. In all, 21 of the 24 patients had objectively measurable disease and were also evaluable for response as follows: 1 complete response, 2 partial responses, 1 case of stable disease, and 17 patients with progressive disease.