A program, Hess2FF, has been developed that automatically constructs parameter and topology files to be used in crystallographic refinement for any molecule, based on a Hessian (force-constant) matrix estimated by any method. The program is tested by redefining hetero-compounds in five different proteins: the inhibitor N-methylmesoporphyrin bound to ferrochelatase, the haem group and its axial ligands in cyctochrome c(553), the active-site metal ion in iron superoxide dismutase, the catalytic zinc ion in alcohol dehydrogenase with a bound trifluoroethanol molecule and the 5'-deoxyadenosyl group in methylmalonyl coenzyme A mutase. It is shown that the resulting structures are improved in several aspects. In particular, the free R(free) factor always decreases and it is shown that a 1.70 A structure of cyctochrome c(553) becomes more similar to a high-resolution (0.97 A) structure of the same protein after re-refinement with Hess2FF. Thus, the force field used in crystallographic refinement significantly affects the final structure and therefore should be published together with the structure to ensure reproducibility. Various methods of obtaining the Hessian matrix employed by Hess2FF are discussed and some recommendations are given. Hess2FF allows the user to divide the atoms of the molecule into atom types that share the same force-field parameters. However, it seems to be favourable to assign a separate type to each atom, which can be performed automatically.