Freshwater fishes varied morphologically, but genetic assessments need some clarification. The present study is carried out to illustrate genetic variations between the freshwater fishes; Malapterurus electricus (Gmelin, 1789),  Synodontis schall  (Bloch & Schneider, 1801),   Labeo niloticus (Forsskål, 1775), and Lates  niloticus as well as the brain isoenzymes electrophoresis of lactic dehydrogenase and glucose-6-phosphate dehydrogenase.  The fishes were collected from River Nile were investigated for brain isoenzyme electrophoresis of lactic dehydrogenase and glucose-6-phosphate dehydrogenase and genetic variation using ten primers. The result of the study showed variations in the expression of the assayed isoenzyme electrophoresis. Also, the application of the RAPD PCR using 10 primers revealed marked variations between the studied fishes. The primer OPB-3 expressed the production of nine unique bands between the study fishes, Nevertheless, OPA-2 and OPB-7 led to the production of eight unique bands, while the primers of OPA-5, OPA-7, OPA-9 and OPB-8 exhibited seven unique bands. Finally, the authors concluded that fish species varied in genetic expression and isoenzymes activities especially lactic dehydrogenase and glucose-6-phosphate dehydrogenase of the studied freshwater fishes.