The evacuation process of a gas mixture in the molecular flow range is characterized by the fact that each gas type is separately pumped at its own respective pumping speed. Since the pumping speeds for most high-vacuum pumps depend on the individual gas type and, further, since the molecular gas-flow conductance is dependent on the inverse square-root-of-mass behavior, gas fractionation occurs. This merely means that the gases which have higher pumping speed are removed faster leaving the gases with lower speed as the predominant residuals. By far, the most common occurrence of gas fractionation is during the evacuation of almost every high-vacuum system. While gas fractionation is most predominant in the molecular flow range, it also occurs in the transition range where the gas-flow behavior is mathematically more complex. The net result of gas fractionation is that the relative composition of the residual gas in the vacuum system steadily changes with time during pumpdown. Since the mathematical aspects of gas fractionation are well established, it seems reasonable that this phenomenon should be simulated in modern computer programs which otherwise simulate the normal vacuum system behavior of gas flow as a function of pressure and of system pressure as a function of time. This article discusses some of the complex interacting problems as well as a final solution which was applied to a specific commercial vacuum-system-design computer program, VSD-II.