This study evaluated the absorption, distribution, and excretion of orteronel, an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. Six healthy male subjects received a single 400-mg dose of radiolabeled [14C]-orteronel (18.5 kBq). The pharmacokinetics of [14C]-radioactivity, orteronel, and the primary metabolite M-I were characterized by ultra-performance liquid chromatography–tandem mass spectrometry, and mass balance recovery of [14C]-radioactivity was determined by liquid scintillation counting and accelerator mass spectrometry. Median time to maximum observed concentration of [14C]-radioactivity was 2.5 hours (plasma/whole blood) and of orteronel was 1 hour (plasma). Mean terminal half-life for [14C]-radioactivity in plasma and whole blood was 9.46 and 7.39 hours, respectively. For [14C]-radioactivity, the geometric mean whole blood–to–plasma ratios for maximum observed plasma/whole-blood concentration, area under the plasma concentration–time curve from time 0 to last quantifiable concentration (AUC0–last), and AUC0–inf (AUC from time 0 to infinity) were 1.04, 0.92, and 0.93, respectively. Dose recovery accounted for 95.9% of the administered orteronel dose; the majority of excretion occurred by 96 hours postdose. The principal excretion route was via urine (mean, 77.5%; including 49.7% unchanged drug and 16.3% M-I) compared with 18.4% via feces. Three mild adverse events were reported; none were considered serious or related to orteronel.