The metabolism and disposition of bucromarone, labeled with 14C on the chromone group, has been investigated in C3H mice and Wistar rats. In separate experiments, animals received 4.4 mmol/kg, iv or po, [14C]bucromarone hydrochloride or succinate. More than 90% of the administered radioactivity was excreted in bile, after iv and po administration. Less than 5 min after iv injection, radioactivity concentrated in all tissues, and blood concentration became very low as compared with its initial level. After po administration, no more than 10% of the dose was incorporated in the tissues. The discrepancy between the high biliary excretion and the low tissue and blood concentration after po administration suggested that bucromarone was well absorbed through the gastrointestinal tract; but after liver uptake, drug and its metabolites were excreted in the bile, less than 10% being distributed into the extrahepatic blood. Comparison of the iv and po areas under the plasma 14C-radioactivity concentration-time curves indicated a poor bioavailability of the molecule after po administration. Analysis of the radioactivity content of bile showed that bucromarone was extensively metabolized after both administration routes. Unchanged bucromarone and three main metabolites, monodesbutylbucromarone, didesbutyl bucromarone, and 2-(3-5-dimethyl-4-hydroxybenzoyl) chromone, amounting to 85% of the bile radioactivity, were identified by HPLC and mass spectrometry. These findings are consistent with a dealkylation of the N-dibutyl group, yielding potential pharmacologically active metabolites monodesbutyl and didesbutyl bucromarone.