The bile salt-nondependent fraction of canalicular bile water has been measured by the extrapolation to zero of the regression line representing the relationship between bile flow and bile salt secretion. This extrapolation assumes that the secretion of bile salts whatever their concentration, carries the same amount of water per molecule. The purpose of this study was to test this assumption. Rats were depleted of bile salts by a bile fistula and infused with sodium taurocholate at rates varying from 30 to 500 mmumol/min. Bile salt secretion was linear with bile salt infusion at any concentration. Values of bile flow and bile salt secretion were grouped according to bile salt concentration, and regression lines calculated. The slopes of the regression lines changed from 0.090 at bile salt concentrations below 10 mM to 0.012 at bile salt concentrations between 30 and 45 mM, (p less than 0.001). These results indicate that the relationship between bile flow and bile salt secretion in the rat cannot be represented by only one regression line. Consequently, the rate of secretion of the bile salt-nondependent fraction of canalicular bile water cannot be measured by the extrapolation of this single regression line.