Pharmacokinetic studies were carried out in 25 patients with advanced cancer receiving deoxyspergualin (DSG), a candidate anticancer agent, in a dose-finding Phase I study. The dosage range explored was 80 to 2160 mg/m2/day for 5 days by continuous i.v. infusion. The drug levels in plasma and urine were measured by high-performance liquid chromatography with postcolumn derivatization and fluorescence detection. One drug metabolite was demonstrated in plasma and urine of treated patients. This metabolite was extracted from urine and purified to homogeneity; thereafter, it was examined by high-performance liquid chromatography, nuclear magnetic resonance, and fragmentation mass spectrometry and was demonstrated to be identical to chemically synthesized desaminopropyl-DSG. The mean steady state plasma concentrations of DSG ranged from 0.28 to 11.1 microM at, respectively, the 80- and 2160-mg/m2 dosage levels. The plasma concentration at steady state and the area under the plasma concentration versus time curve of DSG were proportional to dose (r = 0.97). Following discontinuance of the infusion, DSG was cleared from the plasma in a biexponential fashion. The mean total body clearance was 364 +/- 78 ml/min/m2. Desaminopropyl-DSG was formed extensively at all dosage levels; mean steady state plasma levels of this metabolite reached a plateau 2.65 microM at a dose of 720 mg/m2/day and did not rise with further dose increments. The urinary content of DSG was examined in 20 patients over the dosage range from 160 to 960 mg/m2/day; in this group less than 10% of the administered dose was excreted as DSG. In four patients at the 720- and 960-mg/m2/day dosage levels, the total DSG plus metabolite excretion ranged from 7 to 18% of the administered dose, with comparable quantities occurring as the parent drug and desaminopropyl-DSG.