The electronegativity equalization methodology, EEM, is frequently used to calculate the charge distribution and reactivity index (e.g., local softness and hardness, condensed Fukui function) of molecules. However, recent work (Chelli, R. et al., J. Chem. Phys. 1999, 111, 8569) has shown a serious shortcoming of EEM in the prediction of the polarizability for large molecules. In this paper, our goal is to show that we can obtain a reliable dipole moment for polypeptides in vacuum and continuum-dielectric solvent using the constrained charge approximation and the generalized Born-electronegativity equalization method. Different EEM parameterizations were tested and compared to the expected values of the dipole moment vector operator as calculated at the ab initio B3LYP/6-311G(d,p) level. One EEM parameterization (Bakowies, D., Thiel, W., J. Comput. Chem. 1996, 17, 87) when used with the constrained charge approximation and the generalized Born-electronegativity equalization method was comparable to the CM1 charge model (Storer et al., J. Comput.-Aided Mol. Des. 1995, 9, 87) in the prediction of the dipole moment vector in vacuum and continuum-dielectric solvent, but was calculated with a much greater computational efficiency.