Technical Abstract: A two-dimensional infiltration experiment was conducted to investigate and quantify the effect of spatial wettability variations on DNAPL migration and entrapment in saturated sands. Visual observations of tetrachloroethylene (PCE) infiltration show that organic-wet sand lenses act as very effective capillary barriers, retaining PCE and inhibiting its downward migration. At the end of the PCE infiltration and redistribution event, high PCE saturations were present in the organic-wet lenses, whereas low residual PCE saturations were present in the exposed water-wet sands. A multiphase numerical simulator, previously modified to account for the influence of wettability variations on hydraulic property relations, was used to model this sand box experiment. The simulator incorporates wettability-modified van Genuchten and Brooks-Corey capillary pressure/saturation relationships as well as Burdine and Mualem relative permeability relationships. Although both relative permeability models were qualitatively able to predict the observed PCE retention in the organic-wet layers, simulations with the Mualem model failed to capture the observed rate of PCE migration. A traditional multiphase simulator, incorporating water-wet capillary retention relations, failed to predict both observed PCE pathways and retention behavior. This study illustrates the potential influence of subsurface wettability variations on DNAPL migration and entrapment and supports the use of modified capillary relations in conjunction with the Burdine model for multiphase migration predictions in chemically heterogeneous environments.