E7070 is a novel sulfonamide anticancer agent that arrests the G1/S phase of the cell cycle. Preclinical and phase I studies have demonstrated non-linear pharmacokinetics of the drug. The objective of this study was to quantify the excretion of E7070 and the metabolite 1,4-benzene-sulfonamide (M1) in cancer patients. E7070 (1000 mg) radiolabeled by14C in the benzene disulfonamide moiety (cohort 1,n=6) or in the indole moiety (cohort 2,n=7) was i.v. infused over 1 h. The levels of radioactivity in plasma, red blood cells, urine and feces were determined by liquid scintillation counting, and the E7070 and M1 concentrations in plasma, urine and feces were determined by coupled liquid chromatography–tandem mass spectrometry (LC/ESI-MS/MS). In plasma, the mean area under the concentration–time curve (AUC) based on radio-activity measurements (32.5 and 28.9 h · mM in cohorts 1 and 2, respectively) was substantially higher than the mean AUC of E7070 (3.8 h · mmol/l) and M1 (0.1 h · mmol/l) in all patients. The excretion of radioactivity (mean±SD) as a percentage of administered radioactivity was higher in urine [63.7±9.8% (cohort 1) and 61.5±5.5% (cohort 2)] than in feces [22.7±2.6% (1) and 21.1±3.1% (2)] during a mean collection period of 11 days. In both cohorts, the contribution of urinary and fecal recovery of E7070 (2.3 and 2.7%, respectively) and M1 (5.3 and 5.1%, respectively) was low. Subsequent HPLC analysis with online radioisotope detection of urine showed that the high radioactivity levels are caused by compounds other than E7070 and M1. The major metabolite is formed by glucuronidation of a hydroxylated metabolite of E7070. In conclusion, the excretion of the benzene sulfonamide and the indole moieties of E7070 was the same with a higher renal than gastrointestinal excretion. E7070 is extensively converted into currently unidentified metabolites. Glucuronidation is a major metabolic pathway.