The African buffalo (Syncerus caffer) is a member of one of Africa’s most well known tourist attractions and unique grouping of mammals – the ‘big five’. Historical records indicate that during the 19th century approximately 3 million African buffaloes inhabited almost the whole of sub-Saharan Africa. Several factors such as disease, habitat fragmentation, over-hunting and drought reduced the buffalo population to approximately 400 000 by 1990. The African buffalo is host to a variety of sub-acute diseases, such as bovine tuberculosis (BTB), foot-and-mouth disease (FMD) and corridor disease (CD). Disease is an important factor which influenced African buffalo populations throughout the continent and more specifically the Kruger National Park (KNP) and is largely responsible for the fact that buffaloes are restricted to enclosed areas with strict regulations imposed on their movement. The social organization of animals influences the distribution and spread of a disease - especially in the case of the African buffalo in the KNP. The emergence of BTB in the largest conservation area in South Africa (the KNP), threatens wild and domestic animals and humans who are in close proximity to the Park. The potential economic losses associated with this disease are excessive. The results presented in this thesis provide baseline information into the genetic status of sampled African buffaloes in the KNP, genetic relatedness between sampled individuals as well as BTB associations between sampled African buffaloes in the KNP, based on a limited dataset of 181 animals. Twelve microsatellite markers were used to evaluate 181 samples which were collected from 39 locations dispersed throughout the KNP. Specific population genetic parameters revealed information based on the intra and inter - relationships at the ‘per population’ level as well as at the ‘per prevalence group’ level. Evidence indicates a medium to high level of genetic diversity, a low to medium level of inbreeding (inbreeding coefficient (Fis) for each group ranges between 0.143 and 0.147) and a relatively high level of migration for buffaloes associated with each prevalence group. Pairwise relatedness estimates were determined between individuals, to reveal their level of relatedness (unrelated, full siblings, parent-offspring or half siblings), based on Queller and Goodnight’s (1989) coefficient of relatedness. Relatedness was determined on different levels, intra and interpopulation level, BTB infected and BTB uninfected group level as well as prevalence group levels. Evaluation of data based on these different levels and between different groups, painted an overall picture of the disease condition and genetic relatedness within and between sampled BTB infected and BTB uninfected buffaloes. Evidence indicated that the greater majority of our sampled African buffaloes (BTB infected or uninfected), were genetically unrelated (in terms of sibling and parent-offspring relationships), irrespective of their disease status. M. bovis infected buffaloes sampled and used in our study are not more closely related to each other than to uninfected buffaloes in the same population or prevalence group.