A phase II study was conducted to evaluate the activity and toxicity of 96-hour infusional paclitaxel in patients with previously untreated metastatic colorectal cancer. Twelve patients were enrolled in this study. The first patient received a total dose of 140 mg/m2 over 96 hours resulting in grade 4 neutropenia, neutropenic fever, and grade 3 stomatitis. Subsequent patients received a total dose of 120 mg/m2 over 96 hours. Grade 3 to 4 neutropenia occurred in four of these patients. No significant thrombocytopenia was observed. Grade 3 to 4 nonhematologic toxicities in the group treated at 120 mg/m2 over 96 hours included nausea/vomiting in one patient, stomatitis in one patient, and diarrhea in two patients. One patient experienced a possible pulmonary hypersensitivity reaction. None of the 12 patients achieved an objective response. Two patients had stable disease and ten had progressive disease. Pharmacokinetic parameters including maximum plasma concentration and area under the concentration time curve were significantly higher in patients with grade 3 to 4 neutropenia than patients who experienced less toxicity. The authors conclude that further study of 96-hour infusional paclitaxel in patients with metastatic colorectal carcinoma is not warranted.