The Southwest Oncology Group conducted a phase II study of anguidine in 134 patients with gastrointestinal malignancies. Anguidine was administered as a 4-hour infusion at doses of 3.0 and 4.5 mg/m2 daily x 5. Response rates for patients with colon carcinoma were 22% (four of 18 patients without previous chemotherapy) and 6% (four of 63 patients with previous chemotherapy). There were no responses in patients with pancreatic cancer (four patients) or gastric cancer (six). Toxic effects included thrombocytopenia (19.8%), leukopenia (18.8%), nausea and vomiting (49%), hypotension (37%), and confusion (12%). Antitumor activity of anguidine in patients with colon cancer may be similar to that of 5-FU, but nonhematologic toxicity is substantial.