Vindesine, a newer vinca alkaloid derivative, underwent a phase I clinical evaluation in 68 humans with advanced, refractory malignancies. Patients received single total doses ranging from 2-12.5 mg, repeated every 1-2 wk. Dose-limiting myelosuppressive, gastrointestinal and neurologic toxic effects were observed at higher doses. They consisted predominantly of neutropenia, constipation leading, on occasion, to paralytic ileus and peripheral neuropathy. Total doses of 7.5-10 mg (equivalent to 4-5 mg/m2), repeated every 2 wk, were well-tolerated. There were 2 partial remissions in patients with acute leukemia and prior vincristine therapy, 2 minor responses in patients with renal cell carcinoma, 1 minor response in a patient with squamous cell carcinoma of the esophagus and 1 minor response in a patient with squamous cell carcinoma of the lung. Vindesine is well-tolerated by man, although it shares some of the toxic manifestations of vinblastine and vincristine. Its efficacy in some patients who were no longer responsive to vincristine therapy suggests a lack of clinical cross-resistance between these compounds.