Ursodeoxycholic acid (UDCA) is a nontoxic bile acid currently used in the treatment of different cholestatic diseases. This bile acid is also considered to be a ‘hypercholeretic bile acid’. The effects of daily administration of UDCA on bile flow and the bile acid secretion rate in man are not fully known. The aim of this study was to explore the effects by UDCA on bile flow and its different fractions. The biliary clearances of polyethylene glycol 900 (PEG 900) and mannitol were measured simultaneously in patients with an indwelling T tube after cholecystectomy. One group (n = 6) were given UDCA (10 mg/kg/day) for at least 14 days before the investigation and a control group (n = 8) received no bile acid treatment. The bile secretion was studied in acute experiments where bile was drained for 6 h. The bile plasma ratio for PEG 900 was 31 and that for mannitol was 0.7 which corresponds well with the results obtained in different animal species. The relationship between bile flow and the bile salt secretion rate, as expressed by linear regression analysis, showed no difference between the 2 groups (control y = 0.22 + 0.012x, r = 0.61, p < 0.001; UDCAy = 0.20 + 0.016x, r = 0.88, p < 0.001). The relationship between the biliary clearance of PEG 900 and the bile salt secretion rate, as expressed with linear regression analysis, showed a significantly steeper slope for the UDCA-treated patients (control y = 8.1 + 0.34x, r = 0.41, p < 0.05; UDCA y = 5 + 1.58x, r = 0.78, p < 0.001). No difference in the biliary clearance of mannitol was noted. Daily administration of UDCA did not increase bile flow or the bile salt secretion rate, but clearly enhanced the biliary clearance of PEG 900. One possible explanation for this finding is that UDCA increases the canalicular influx of water due to cholehepatic shunting of this bile acid.