ABSTRACTObjective:We tested the hypothesis that the measurement volume of the laser Doppler flowmeter (LDF) is too small to provide reliable quantitative estimates of total liver blood flow of large mammals, such as the pig.Methods:In a perfused pig liver, the influence of changing (i) hepatic arterial (HA) and portal venous flows individually (n= 9), (ii) HA flow at fixed portal venous flow (50%, 70%, and 100% expected total liver blood flow), and (iii) hematocrit (0–30%) at fixed total liver blood flow on LDF flux was tested (n= 8).Results:Linearity of LDF with hepatic arterial flow and portal venous flow was confirmed; however, the slope of the regression lines was higher for hepatic artery [1.92 ± 0.60 (SD)] than portal vein perfused livers (0.66 ± 0.34;P30%. At constant total liver blood flow (100 ml/min per 100 g), LDF response decreased linearly by a factor of about 2 on changing the hematocrit from 30% to 5% and markedly fell as the hematocrit was further decreased to zero.Conclusions:These results suggest that (i) the LDF flux signal from the liver surface provides a poor measure of hepatic microcirculatory blood flow during changes in total liver blood flow as the LDF responds with about three times greater sensitivity to changes in hepatic arterial than in portal venous flow, and (ii) when hematocrit is falling, LDF may underestimate hepatic perfusion to a significant extent. In addition, due to high measurement variability, the LDF flux signal cannot be quantified in absolute perfusion un