The excretion, distribution, and metabolism of ftorafur was studied in rats following a single intravenous injection of radioactively labeled drug. Approximately 55% of the administered radioactivity was excreted as 14CO2, while 23% was eliminated via the urinary route in 24 hr. Less than 2% was excreted in the feces. The major excretory product found in the urine was unmetabolized ftorafur. However, the proportions of radioactively labeled metabolites such as 5-fluorouracil and urea increased with time after injection. The half-life of ftorafur in plasma was estimated to be approximately 5 hr. The drug was fairly evenly distributed to liver, small intestine, spleen, kidney, and brain. Highest initial concentrations were found in the liver, which also retained more drug for a longer period than the other tissues. The liver was also found to contain the highest initial proportions of 5-fluorouracil and its metabolites. The results obtained are consistent with the suggestion that ftorafur may be a depot form of 5-fluorouracil and that the liver may be the primary site at which the latter drug is released in vivo.