A new semiquantitative measure of the difference between two electron density distributions is proposed. Specifically, the natural orbitals of an accurate electron density, such as those given by a configuration interaction method, are used to expand the Kohn-Sham orbitals of an approximate density functional method. The difference between the two density distributions is then reduced to a single number, the orbital-based density difference index (DDI). With the reference densities calculated from quadratic configuration interaction calculations including single and double substitutions, DDIs were obtained for four diatomic molecules using three basis sets and seven approximate functionals. Results are also included for an additional six small molecules with a flexible extended basis set and the same set of functionals. These results show that the DDI leads to conclusions that are consistent with those obtained previously by visual comparison of density difference plots. The orbital-based density difference indices are very dependent on the choice of the functional, but are fairly stable with respect to the choice of the basis set. (C) 1997 American Institute of Physics. [S0021-9606(97)00441-8].