An approximate method is evaluated for calculating the second virial coefficient in a dilute macromolecular solution bounded by two interfaces. The approximation is essentially the superposition of the coefficients calculated independently for each surface. To test this approach, the depletion interaction between two particles in a solution of nonadsorbing, spherical macromolecules is calculated in systems with either hard-wall or long-range electrostatic interactions. In all systems tested, the interparticle interaction energy calculated with the approximation is found to be in good agreement with that calculated using the exact approach (e.g., error less than 2% at the smallest separations). The primary advantage of this approximation is a significant reduction in the computation time required for calculating the depletion interaction, especially in charged systems. The paper also shows that the expressions for predicting the depletion interaction in purely hard-sphere systems can be used in dilute ionic systems, provided the appropriate effective macromolecule size is used. For the attractive depletion interaction, this effective size is determined by the range of the particle-macromolecule interaction (as opposed to the macromolecule-macromolecule interaction). (C) 2003 Elsevier Science (USA). All rights reserved.