The sharp tooth catfish (Clarias gariepinus) is one of the most important fresh water fishes in the River Nile in Egypt. Ninty-four samples of alive mature catfish, Clarias gariepinus. were collected from the tributaries of River Nile, Egypt during summer and winter seasons of 2008- 2009. Both healthy and diseased fish were examined macroscopically for skin and gill disease. The skin and gill of both healthy and diseased fish were subjected for microbiological identification of pathogenic bacteria, SDS-PAGE and DNA fragmentation analysis and light, scanning and electron microscopic investigation. The infected fishes possess ulcerative and haemorrhagic skin patches more intensified in winter more than summer. The isolated bacteria from both gills and skin of diseased were Actinobacter lwoffii, Enterobacter amnigenus , Escherichia coli , Citrobacter amlonaticus , Serratia odorifera and Aeromonas jandaei (gramnegative ), Staphylococcus epidermidis (Gram-Positive ). SDS-PAGE revealed no variations between healthy and diseased skin and gills. However, DNA fragmentation was moderately detected in diseased skin more than of the gill. Scanning electron microscopic examination (SEM) revealed necrotic patches in both skin and gills. Light microscopic study possesses massive atrophy, thinning and degenerative changes of both skin and gill. Transmission electron microscopic (TEM) study exhibited abundant distribution of cytoplasmic vacuoles as well as alterations of cytoplasmic organelles including mitochondria, rough endoplasmic reticulum and lysosomes of club cells and epithelial cells. The nuclear envelope of both club and epithelial become convoluted. The mucous cells showed widespread of vacuoles. The macrophage cells were apparently become degenerated. The epidermal-dermal junction lacked irregular pattern and the dermis exhibit internal haemorrhage and hyaline necrosis. Finally, C. gariepinus is highly susceptible to bacterial infection inducing pathological alterations in skin and gills of fishes and may cause mortality of it
