A strategy allowing the computation of sorption isotherms, up to high penetrant activities, in glassy, matrices has been designed. The new scheme permits an equilibrium repartition of the solute molecules in the matrix. The scheme is coupled to an efficient methodology for the calculation of the penetrant fugacity, namely, the direct particle deletion method, a generalization of the staged particle deletion method. The sorption isotherms of CO2 in atactic polystyrene (PS) and the induced polymer swelling have been calculated in the temperature range from 308 to 405 K for pressures up to 300 bar. The results compare favorably to available experimental data. Larger deviations are observed at low temperatures and high pressures, most probably due to the long relaxation times of the polymer matrix. Derivative properties, such as the partial molar volume and the partial molar enthalpy Of CO2, have been calculated in good agreement with experimental findings. The segmental dynamics of PS have been analyzed, and the pressure-induced glass transition (P-g) has been calculated for various temperatures below the T-g of pure PS. The results compare well with experimental data. The analysis of the free volume of the polymer matrix in the CO2/PS systems showed higher free volumes at higher temperatures because of polymer swelling.