Fourteen patients with progressive localized tumors were treated on a clinical and pharmacological study with intra-arterial Thiotepa. A transfemoral percutaneous catheter was inserted into the major artery supplying the tumor. A venous catheter was inserted into the vein draining the tumor area for blood sampling. Doses of Thiotepa ranged from 0.3 mg/kg to 1.0 mg/kg. Courses were repeated monthly and doses of drug escalated as tolerated. Toxicity was mild and doses of drug at least up to 0.9-1.0 mg/kg were tolerable. Pharmacokinetic parameters suggest increasing binding of Thiotepa to tissue when the drug is administered by the intra-arterial route. Clinical responses were observed in a patient with melanoma and in another patient with unknown primary cancer.