The goal of this study was to determine the most appropriate hydrodynamic model for the Loc-I-Gut in-vivo perfusion system. The general mixing-tank-in-series model, which can approximate single mixing tank and laminar and plug-flow hydrodynamics, was fitted to the observed experimental residence-time distribution curves for the non-absorbable marker [14C]PEG 4000. The residence-time distribution analysis shows that the hydrodynamics of the perfusion solution within the jejunal segment in man is well approximately by a model containing on average between 1-2 mixing tanks in series. The solution is well mixed when using perfusion rates of 2.0, 3.0 and 6.0 mL min-1. The average mean residence time estimates from the fitted residence-time distribution were 12 +/- 7.6, 15 +/- 4.2 and 7.7 +/- 4.6 min, respectively, at these three perfusion rates. The mean volumes of the segment (Vs) were 25 +/- 15, 45 +/- 12 and 46 +/- 27 mL, respectively. There were no statistical differences between 2.0, 3.0 and 6.0 mL min-1 in respect of the number of mixing tanks (n) and mean residence times. This residence-time distribution analysis indicates that the luminal fluid in the Loc-I-Gut perfusion system is well-mixed, and that permeability calculations based on the well-mixed assumption most closely approximate the actual local (average) membrane permeability within the perfused segment.