A macroscopic approach for calculation of electrostatic interactions in proteins, initially developed for solution, was extended to describe isolated multiply-charged protein ions in the gas phase. It was combined with a Monte Carlo algorithm for determination of the most probable protonated sites for a different charge. Several quantities characterizing the behavior of protein ions in vacuum were calculated for nativelike lysozyme and ubiquitin. Among these are the apparent gas-phase basicity for various charge states, as well as the intrinsic basicities and the probabilities of protonation of individual sites. The contributions of the intramolecular solvation term and the peptide dipole-charge interactions to the intrinsic gas-phase basicity of each site were estimated. It was shown that the peptide dipoles may essentially influence the intrinsic gas-phase basicity of individual protonation sites. The approach can be successfully used to probe electrostatic interactions of gas-phase protein ions, provided information on the three-dimensional structure of these ions is available.