A force balance approach is used to calculate the depletion force between two charged spheres in a solution of charged spherical macromolecules. When compared to the case of hard sphere interactions only, the presence of a long-range electrostatic repulsion increases greatly both the magnitude and range of the depletion effect. In addition, a virial expansion of the single particle distribution function, correct to O(rho(infinity)(2)), is used to estimate the second-order effects arising from two-body macromolecule interactions. It is found that even at concentrations as small as 1% volume, a depletion repulsion can arise as two particles first approach. Upon closer approach, the force switches sign and a significant depletion attraction results. This effect is similar qualitatively to results obtained using nonadsorbing uncharged, flexible macromolecules. However, both the range and magnitude of the force produced by charged spheres are much greater (e.g., interaction energies exceeding 1 kT are predicted at separation distances as large as 13 Debye lengths). Depending on the macromolecule concentration, the depletion effect can either promote stability of a colloidal dispersion or induce flocculation.