The residues of several organochlorine and pyrethroid pesticides were measured in the gills and intestine of Oreochromis niloticus and Mugil cephalus that were collected from three fish farms at El-Fayoum Governorate, during spring 2006. The impact of the accumulated pesticides on the total proteins, total lipids and the histological structure of the gills and intestine was studied. The results showed the existence of a wide variety of organochlorine pesticides residues (a-HCH, y-HCH, Aldrin, Heptachlor, Dicofol, Chlordane, Dieldrin, Endrin and o,p-DDT) and pyrethroid pesticides residues (Thiram, Pencycuron, Atrazine, Butachlor, Diniconazole, Cypermethrin and Fenvalerate) in the gills and intestine of both fishes. The total protein and lipid contents in the gills and intestine of the studied fishes from the three fish farms showed a highly significant decline. Moreover, several histopathological alterations as severe degenerative, necrotic and proliferative changes were observed in the gill filaments and secondary lamellae. Furthermore, edema, curling and atrophy in secondary lamellae, as well as dilation and congestion in the blood vessels of gill filaments and haemorrhage between gill filaments were noticed. On the other hand, the intestine showed severe degenerative and necrotic changes in different intestinal layers with aggregation of necrotized cells in the intestinal lumen, atrophy in the muscularis, haemorrhage in the submucosa, edema between the intestinal layers, increased goblet cell population and dilation in the blood vessels of the submucosa.