ONE electrophoresis affords a simple, rapid technique for comparing and characterizing proteins. It is especially suitable for investigations of genetically altered proteins, and notable results have come from the use of this method in studying hemoglobins (INGRAM 1961 ) and haptoglobins ( CONNELL, DIXON and SMITHIES 1962). Drosophila melanogaster is extraordinary in terms of the extensive array of genetic techniques which have been developed for analyses of its genetic system. However, it has seldom provided material for physiological genetic analysis. This is largely true because few biochemical differences, especially protein differences, are readily demonstrable in the organism. For analyzing controlling mechanisms in development, variegated position effects, or other genetic phenomena characteristic of higher organisms, Drosophila melanogaster remains the experimental animal par excellence. The demonstration of protein differences in a system amenable to sophisticated genetic analysis offers unusual opportunity for integrating genetic, biochemical, and developmental approaches at the level of gene action. To this end, methods have been developed for analyzing protein differences in mutant stocks of Drosophila. The techniques employed have also been used with a variety of materials in this laboratory. Over thirty-five species in the genus Drosophila have been analyzed, and the results of this screening will be the subject to a separate paper in this series. Tetrahymena has been analyzed using identical methods, and a large number of migrating protein bands was resolved (DUNHAM 1962). Similar techniques have been successfully employed using embryonic and adult chick brain as the starting material ( WYTTENBACH, personal communication). Thus, the methods to be described here are potentially useful with a broad array of materials and for investigating a wide variety of problems. The report includes a description of the methods employed, the results obtained from the initial screening of mutant stocks, and a preliminary analysis of a protein difference detected in strains of the mutant glass of D. melanogaster.