Irinotecan (CPT-11) is a camptothecin derivative used for the treatment of cancer. It is a prodrug that is metabolized to its active form, SN-38 [(+)-(4S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]- indolizino[1,2-b]quinoline-3,14(4H,12H)-dione]. To clarify the pharmacokinetic difference between CPT-11 and SN-38, the plasma levels, tissue distribution and excretion of SN-38 were investigated after dosing rats with 14C-labeled SN-38. The plasma radioactivity showed bi-exponential decay with a terminal half-life of 9.91 h. TLC separation revealed that the plasma radioactivity consisted mainly of SN-38 at 5 min after dosing; however, it was soon replaced with SN-38 glucuronide (SN-38 Glu) and an unknown metabolite (M-2). The half-life of unchanged SN-38 after dosing with SN-38 was about 7 min, which was much shorter than that after dosing with CPT-11 (2.8 h) as reported previously. Its radioactivity was excreted mainly in feces (70.0% within 168 h), and biliary excretion (64.1% within 48 h) could account for the fecal excretion. The major component of urinary and biliary radioactivity was found by TLC to be SN-38. Whole body autoradiograms revealed that the tissue distribution of the radioactivity was low except in the liver and kidney. The radioactivity decreased rapidly and little was found in the body 24 h after dosing. In conclusion, SN-38 was excreted rapidly from bile and showed poor tissue distribution. These characteristics lead to a shorter SN-38 half-life, more so than dosing with CPT-11.