The present studies were performed to interpret the developmental and genetic aspects of Gpdh^+ locus in Drosophila melanogaster. The activity of GPDH was maintained by the two isozymes (GPDH-1 and GPDH-3), which showed the developmental and tissue-specific expression. The immunological identity suggested that the structural difference between two isozymes was very slight. The immuno-blot analysis of two isozymes in protein and RNA level suggested that GPDH-3 arised from posttranslational modification of single polypeptide (GPDH-1). Also, present study suggested that the turnover rate of two isozymes must take part in developmental and tissue-specific regulation of GPDH activity during Drosophila life cycle. The Gpdh^+ locus of Drosophila melanogaster in natural population was polymorphic in both the allozyme variation and the activity variation. Therefore, the genetic variations of GPDH inspected in this study were discussed.