Studies on the health status of lions (Panthera leo) in the Kruger National Park (KNP) have revealed certain lions suffering from chronic debility (“poor doers”). Clinical signs include chronic emaciation, renal failure and chronic bacterial infections. The diagnosis of Mycobacterium bovis in KNP lions in 1995 raised the question of whether these “poor doer” lions were suffering from tuberculosis. Tests confirmed tuberculosis in some cases, but no aetiology for the poor condition was found in a large percentage of the animals tested. Extensive literature review failed to reveal reports of similar findings of chronic debility in free living lion populations, although various disease outbreaks and infectious diseases of lions are described. These are briefly reviewed. Surveys have confirmed that the majority of the KNP lions are serologically positive for feline immunodeficiency virus (FIV), the clinical importance of which is questioned as a possible cause of immunosuppression in lions. Tissue samples from eleven lions suffering from chronic debility and six clinically healthy lions were studied by light microscopy. Changes in the various organ systems were reported and tabulated with reference to degree and relevance. Frozen lymph node samples from some animals in both groups were collected for immunohistochemical staining for T and B lymphocytes and CD4 and CD8 subsets. In some cases serology was done for FIV using a Puma Lentivirus ELISA and a Puma Lentivirus Western Blot technique. Mycobacterial culture results were available for some animals. The histopathological features varied, but notable changes were seen in the lymph nodes. These included generalized lymphoid hyperplasia (predominantly affecting clinically healthy lions), progressing through combined hyperplasia and atrophy in different nodes to lymphoid atrophy affecting most of the lions suffering from chronic debility. These are non-specific findings seen in various systemic diseases, including canine distemper virus infection and toxoplasmosis, but they have also been described in domestic cats suffering from FIV infection and humans with HIV. Further findings in lymph node sections included mineral deposition and multifocal cystic spaces. Other important histopathological changes included chronic interstitial pneumonia, renal amyloidosis, chronic interstitial nephritis, Wallerian degeneration of the spinal cord, encephalomalacia and anterior uveitis. Two animals suffered from multifocal, multisystemic granulomatous inflammation. Mycobacterium bovis was cultured from one of these cases, but no apparent aetiology could be found in the other. Eosinophilia was a consistent finding in many tissues and most likely related to the high parasite load in many of the animals. Parasites found included Hepatozoon spp., microfilaria, cestodes, nematodes and trematodes and Sarcocystis spp. and Trichinella spp. Immunohistochemical staining for B and T lymphocytes and CD4 and CD8 subsets showed a normal distribution of the staining pattern within the lymph node sections, although the samples were all from FIV positive lions. The histopathology in both study groups was of a non-specific nature and not indicative of any particular disease syndrome, although many of the changes are similar to those described in domestic cats infected with FIV. There are indications of possible immunocompromise in the “poor doer” lions, which warrants further investigation. / Dissertation (MMedVet (Pathology))--University of Pretoria, 2006. / Oral Pathology and Oral Biology / unrestricted