Etoposide (VP16) levels were determined by high-performance liquid chromatography assay in plasma, urine, and surgical specimens of patients with choriocarcinoma undergoing surgery after a dose of 100 or 200 mg/m2 given as a 1-hour infusion. The drug disappeared from plasma biexponentially, with a terminal half-life of 4.1 +/- 0.4 hours, an apparent volume of distribution of 9 +/- 1.1 L/m2, and clearance of 21.5 +/- 3.1 ml/minute/m2. Fifty and 740 minutes after the end of VP16 infusion, the drug concentrations in myometrial carcinoma or in normal myometrium were approximately 40%-50% of those in plasma; 25-180 minutes after the end of drug infusion, the concentrations of VP16 in lung metastases amounted to 19%-43% of those in plasma, whereas in normal lung, the concentrations of VP16 were 38%-61% of those in plasma. In subcutaneous tissue, VP16 levels were much lower than in plasma (about 5%-27%). About 50% of VP16 was eliminated in the urine as unchanged drug, glucuronide, or sulfate.