The PKD has been documented to cause particular economic loss in fish farms worldwide. The present investigation aims to determine the prevalence and the etiology of proliferative kidney disease (PKD) in Oreochromis niloticus and Clarias gariepinus obtained from El-Riah El-Tawfiki and its tributaries. To achieve this goal, 500 fish were used of which 266 were Oreochromis niloticus and 234 were Clarias gariepinus. The fish were dissected and the kidneys were examined macroscopically for the presence of morphological abnormalities and nodules. Fresh and Giemsa-stained slides of kidney tissue were also examined for determination of the causative agent. The results showed the prevalence of PKD in Oreochromis niloticus was higher in autumn (95.08%) and spring (91.94%) than in summer (76 %) and winter (73.53%). The prevalence of PKD in Clarias gariepinus was high in winter season (76%) and low in spring season (36.84 %). The overall prevalence of PKD was higher in oreochromis niloticus (83.46%) than in Clarias gariepinus (46.58%). The Clinical signs of fish affected with PKD may be non-specific included distended abdomen with dark color, anaemia with pale gills and emaciation. Some fish have nodules in the eye around the iris forming a ring. Macroscopically, there was enlargement of the kidney with appearance of some kidney nodules of approximately 0.2 – 0.6 mm diameter. Based on the spore morphology, the causative agent was identified as different types of myxosprean spores in Oreochromis niloticus and Clarias gariepinus. The high prevalence of PKD in both types of fishes suggests the need to establish strict control measure to overcome the great economic losses imposed by the disease.