Identification of macromolecules by zone electrophoresis has usually been based on differences in migration distances under a single set of electrophoretic conditions. Classically, it has taken the form of coelectrophoresis on gel slabs. In “quantitative” polyacrylamide gel electrophoresis (PAGE), separation conditions were standardized sufficiently to allow for identification of macromolecules between experiments on the basis of their relative electrophoretic mobilities, R f ± σ R f . More reliably, molecular identity or distinguishability have been based on several R f values at several gel concentrations (%T) and the linear relationship between log R f and %T, the Ferguson plot. The slope (retardation coefficient K R of this plot is desoriptive of molecular size while the γ-intercept ( Y 0) is a measure of net charge. The joint 95% confidence envelopes for K R and Y 0 may be used as criteria for identification of molecules. Distinction between two molecular species depends on the size and position of the two confidence envelopes or ellipses. By pooling estimates of residual varlance (scatter areund the regression line for the Ferguson plot) for several proteins, it is possible to reduce the size of the ellipses and improve the sensitivity of the method to distinguish elesely related species. The sensitivity of this method depends on the size and reprodueibility of the 95% confidence envelopes, and on the limitatiens in the number of electrophoretic fractionations that one is reasonably willing to invest. Any molecular identification problem therefore raises the implieit question whether to base distinction on migration distance, on R f , or on the joint 95% confidence envelopes for K R and Y 0 and related statistical ( F test) eriteria. Further, in the event of inconsistent answers to the question of molecular distinguishability from the three approaches, we need rational criteria to select the “best” answer. These problems and some solutions are illustrated by the present study which was designed to determine whether the enzymatic digestion products of human growth hormone produced by subtilisin-B are or are not the same as those obtained by digestion with plasmin. It appears that the joint 95% confidence envelopes of K R and Y 0 provide at this time the most discriminating criteria of distinction, indicating significant differences between nearly all the products of plasmin and subtilisin digestion of hGH. However, the lower resolution provided by the R f criteria has the advantage that it allows one to group the products of the partial hydrolysis of hGH into “families” which may be associated with different ranges of specific bioactivities.