A mathematical model of multicomponent permeation systems with high-flux, asymmetric hollow-fiber membranes is presented. The model takes into account the permeate pressure variation inside the fiber. In the special case of negligible permeate pressure drop, the model yields a simple analytical solution for membrane area calculation that eliminates the numerical integration step required in existing methods. Laboratory multicomponent permeation experiments have verified the mathematical model and have demonstrated the technical feasibility of using the high-flux asymmetric cellulose acetate hollow fiber for H2, CO2, and H2S separation. It is shown that the selectivity of the cellulose acetate membrane is ideally suited to the recovery of hydrogen from the purge gas of reactor recycle loops. For the separation of high-concentration CO2 or H2S, the test data show that the permeabilities of the individual components in mixed gas permeation are significantly different from those of pure gases.