We have tested the ability of the OPLS-AA models (optimized potentials for liquid simulations) of alkanes and perfluoroalkanes recently developed by Jorgensen and co-workers to represent the unusual mixing behavior of alkane+perfluoroalkane systems. We find that these all-atom Lennard-Jones (6-12)+Coulomb representations, together with the usual Lorentz-Berthelot combining rules, fail to reproduce the weaker-than-anticipated interactions between these two classes of molecules. Systematic disagreements with experiment are found in the case of second pressure virial coefficients, gas solubilities, and liquid-liquid mixing properties. These discrepancies are not specific to the choice of OPLS-AA potentials, but are rather linked to the failure of the geometric mean combining rule for relating unlike atom interactions. In all cases examined, a reduction in the strength of cross H+F interactions by similar to25% relative to the geometric mean is required in order to achieve reasonable agreement with experiment. Several less commonly used combining rules were also examined. Although some of these rules are able to provide a reasonable description of the interactions among perfluoroalkane and alkane species, they fail to provide a consistent treatment when atoms other than C, H, and F are considered, as is necessary for modeling the interaction of the former molecules with rare-gas atoms. (C) 2003 American Institute of Physics.