A new empirical approach to model the solvent effects in protein-membrane complexes is proposed. The generalized Born (GB) approximation is extended by including an implicit membrane (INI) in the calculation of the electrostatic contribution to the solvation free energy (GB/IM model). In addition, nonpolar solvation energy terms are calculated on the basis of the solvent-accessible surface approximation including the effect of membrane (SA/IM model). The generalized Born -solvent-accessible surface area (GBSA) model with implicit membrane (GBSA/IM) is implemented in the CHARMm package and is applicable for energy calculations and molecular dynamics simulations. The potential of the new method for studying large molecular systems is demonstrated with the example of two transmembrane proteins, bacteriorhodopsin and rhodopsin. The results show a clear directional asymmetry of the solvation energy during translocation of the proteins through the membrane, which is suggested to be an alternative explanation of the known "positive-inside" rule. The method is also tested in nanosecond molecular dynamics (MD) simulations of the influenza virus HA2 (1:20) fusion peptide. Interestingly, when starting from two different initial positions of peptide, during the 3 ns runs, the helical fragment consistently adopts a tilted (similar to20-25degrees) orientation with respect to the membrane in very close agreement with the known electron paramagnetic resonance (EPR) data. We also found an excellent agreement between the pKs of the N-terminal amino group computed for the final MD structures and the known NMR titration data.