alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity against small cell lung cancer and colon cancer in cell culture and animal tumor models. To evaluate clinical efficacy and further define toxic effects of this new agent, phase II trials of DFMO were performed in previously treated patients with advanced small cell lung cancer and previously untreated patients with metastatic colon cancer. Oral DFMO was administered at a dose of 2.25 g/m2/day every 6 hours continuously to patients with small cell lung cancer. The same dose was given to patients with colon cancer but on a schedule of "3 weeks on, 1 week off" to avoid hearing loss. Evaluation of toxicity indicated that thrombocytopenia was seen only in patients receiving continuous DFMO who had received prior chemotherapy, while reversible hearing loss and gastrointestinal side effects occurred on both intermittent and continuous schedules in previously treated and untreated patients.