In the Kruger National Park (KNP), pansteatitis in sharptooth catfish, Clarias gariepinus (Burchell), was shown to be a serious problem in the inlets to large man-made lakes fed by rivers arising in the polluted catchments of the Olifants and Sabie rivers. An increasing prevalence of pansteatitis was recorded in catfish from the Olifants River gorge. A low prevalence was found in catfish upstream of the gorge at two further sites. No pansteatitis was detected in catfish from a rain-filled dam distant from the potential pollution sources affecting the Olifants River and in rivers arising outside of the park that were not dammed. Analysis of stomach content indicated a higher prevalence of fish in the diet of catfish affected by pansteatitis than in those not affected. Significant pathology in catfish was limited to changes associated with a generalised necrosis and inflammation of adipose tissues (pansteatitis), and there was evidence that lesions accumulated over time. Similar pathology was found in a captive population of catfish with known nutritional pansteatitis. Pathology in other organs that might have been attributed to pollution could not be demonstrated. Examination of blood smears and measurement of haematocrit, blood haemoglobin, serum vitamin E and erythrocyte glutathione peroxidase values did not prove useful as monitoring tools, probably because of the episodic exposure to oxidative stress and the chronic nature of the condition. Pansteatitis-affected catfish, kept in an experimental pond for 11 months after the inciting nutritional cause had been removed, retained steatitis lesions almost unaltered. Whereas lipolysis appeared to be reduced by pansteatitis, adipogenesis appeared to be unaffected. Juvenile catfish confined in experimental tanks with sediments from sites where pansteatitis occurred remained healthy, and no pathology developed after 14 months, suggesting that sediments were not directly toxic. The results of the study present the first record of pansteatitis in both wild and farmed African sharptooth catfish and emphasize the ecological importance and complexity of nutritional oxidative stress in a disturbed aquatic environment. Nutrient entrapment and the consumption of phytoplankton-feeding fish rich in polyunsaturated fats, particularly silver carp, Hypophthalmichthys molitrix (Valenciennes), a species alien to Africa but present in the Olifants River, is proposed as the dietary cause of the pansteatitis.