The topoisomerase-1 inhibitor, topotecan, was tested in 48 eligible patients with advanced colorectal cancer. The patients had no prior chemotherapy and a Southwest Oncology Group performance status of 0-2. Topotecan was administered intravenously at 1.5 mg/m2/day for five days and repeated every 21 days. The major toxicity was hematologic with 19 out of 48 (40%) patients having grade IV granulocytopenia and 4 out of 48 (8%) patients demonstrating grade IV thrombocytopenia. Two patients (4%) demonstrated partial response. Thirty patients have died and the Kaplan-Meier estimate of median survival is 9 months (95% confidence interval; 7-16 months). Topotecan in this dose and schedule does not appear active in patients with advanced colorectal cancer.