Nine patients were studied with tritium-labeled EPEG, a new epipodophyllotoxin antineoplastic agent. Four patients received 220 and 5 received 290 mg/sq m body surface area intravenously in 500 ml in 1 hr. Postinfusion plasma decay was biphasic with mean values for the parameters at 220 mg/sq m, A, 25.8 µglml; B, 3.35 µg/ml; α, 0.50 hr−1; β, 0.074 hr−1, and mean values at 290 mg/sq. m, A, 33.7 µg/ml; B, 4.35 µg/ml; α, 0.36 hr−1; ², 0.066 hr−1, Mean volume of distribution was 32.07% of body weight. Urinary recovery was 43.5%, of which 66.8% was unchanged drug. Penetration of drug into the cerebrospinal fluid was poor. The results indicate that both renal excretion and metabolism are important for elimination of the drug.