Prior studies have begun to examine the sensitivity of binding enthalpies to the choice of force field parameters . Interestingly, enthalpies seem to be more sensitive to force field details than are binding free energies. For example, binding free energy calculations for ∼40 cyclodextrin-guest systems, with 10 different force field and water model choices, yielded a range of root-mean-square error (RMSE) values, relative to experiment, of 0.85 to 1.80 kcal/mol; whereas the corresponding range of RMSE values for the binding enthalpies was 0.92 to 4.0 kcal/mol . We have also observed surprisingly strong sensitivity of host-guest binding enthalpies to the choice of water model . If it is in general true, as we suspect, that enthalpies are more sensitive to force field parameters than are free energies, this would represent a purely in silico case of entropy-enthalpy compensation.