Abstract: A comparison between the linear combination method (LCM) and the orthogonal function method, both being computational spectrophotometry, was made by determining ephedrine HCl in the presence of the interference of lactose. The results indicate that, the accuracy of the former was ten times that of the latter, which evidenced, not only in theory but also in practice, the advantage of LCM in improvement of accuracy. In addition, the effect of the number of determined points and the accuracy of some points on the total accuracy in LCM was discussed. The optimum form of LCM was given and they evidenced the advantage of LCM in simplicity and convenience.