A perturbation approach based on the generalized molecular interaction potential with polarization (GMIPp) has been developed for combined quantum mechanical and molecular mechanical (QM/MM) simulations of solutions. A unique feature of the method is to avoid repeated self-consistent field calculations for each new solvent configuration during the fluid simulation. The results show that the GMIPp potential coupled to Monte Carlo simulations yields similar energetic and structural results for a series of 14 organic compounds in aqueous solution in comparison with the results obtained from full ab initio QM/MM simulations at the HF/6-31G(d) level. Importantly, the solute electronic polarization energy is reasonably estimated by the GMIPp method. The implementation of the GMIPp within the Monte Carlo simulation framework appears to be a promising computational strategy for carrying out QM/MM calculations for large molecules, which otherwise would be difficult by using standard QM/MM techniques.