The clearance of 14C-mannitol in the bile before and during intravenous secretin was measured in anesthetized dogs receiving a constant infusion of taurocholate. During secretin, bile flow (+80%) and bicarbonate output (+140%) both rose while bile salt output was unchanged (+2.4%). Mannitol clearance increased significantly by 20 +/- 8% (P less than 0.05). The ratio of bile salt output to mannitol clearance fell significantly after secretin by 14 +/- 7% (P less than 0.01). Secretin caused, therefore, a significant rise in mannitol clearance in this canine preparation. This may be due either to a rise in the bile salt independent fraction of canalicular bile or to tubular entry of mannitol.