The pharmacology of 4'-demethylepipodophyllotoxin 9-(4, 6-0-thenylidene-β-Dglucopyranoside) PTG, a new anticancer drug, is reported. Six patients with advanced cancer were treated witli PTG (67 mg/m2 of body surface area intravenously) specifically labeled with tritium as the first dose of a weekly × 6 course. Recovery of drug in the urine was 44.49 ± 8.2% ofthe administered dose in 72 hr, of which 78.7 ± 5.1% was metabolite. Recovery in thefeces was 0 to 10.05% in 4 patients. Plasma decay fitted the equation Cp = Ae-αt + Be-βt + Ce-yt by nonlinear least-squares regression. Mean values for the parameters (after infusion) were A 14.3 ± 5.5, B 9.66 ± 3.98, C 2.44 ± 1.33 µg/ml; α 2.05 ± 1.25, β0.26 ± 0.15, σ 0.038 ± 0.016 hr-1, Levels of drug in the cerebrospinal fluid (CSF) were 2 consecutive weekly doses) developed leukopenia (WBC 3). Mean nadir of WBC was 3,600/mm3. The most marked leukopenia (WBC, 2,300/mm3) was seen in the patient with the longest terminal phase plasma half-life (38.5 hr). Two of 5 patients evaluable for response received clinical benefit (1 laryngeal carcinoma, 1 histiocytic lymphoma). It is concluded that PTG has a long terminal phase half-life (11-38.5 hr), is largely metabolized, and does not penetrate the normal blood-brain barrier.