Bubonic plague, caused by the bacterium Yersinia pestis, is a zoonose that prevails in small mammals and is transmitted by their ectoparasites, i.e. fleas. The disease occurs in natural foci spread all over the world. Up to present, the ecology of plague is still unknown; more specifically, the mechanisms that determine the presence of bubonic plague in specific regions are not well understood. This study aims at (1) contributing to the better understanding of the mechanisms that determine the presence of plague in certain regions, (2) establishing underlying ecological factors that influence the occurrence of plague and (3) identifying areas of potential plague risk in Africa. However, there is only little scientific knowledge to go by, it is difficult to formulate specific hypotheses, and consequently, also difficult to stipulate an exact scale level to work on. Therefore, the phenomena plague is studied on three different scale levels. On the first level - the continental level -, the distribution of plague is considered on the continent Africa. During the last decades, Africa was characterized by a very high percentage (more then 90%) of all human plague cases. The plague problem is approached by means of a recent technique used in research concerning the ecology and epidemiology of infectious diseases, Ecological Niche Modeling (ENM). Ecological niches and potential geographic distributions are modelled using the Genetic Algorithm for Rule-set Prediction (GARP). In general GARP focuses on modelling ecologic conditions wherein a species, in this case bubonic plague, can maintain populations without immigration. Specifically, GARP relates ecological characteristics of occurrence points to those of points sampled randomly from the rest of the study region, developing a series of decision rules that best summarize factors associated with presence. As a final result, potential plague distribution areas are identified and demarcated. On the second level, the same ENM-approach is practiced for two endemic plague regions (Lushoto district, in Tanzania and Ituri district, in DRCongo) and their surroundings with this distinction that the resolution from the environmental GIS coverages is higher. In this way, other environmental variables could be studied and moreover, we could examine them in more detail. In addition, specific attention can be drawn to the transition between the plague region and their surroundings. Finally, on the third level, we focus on some villages in Lushoto district. Abiotic and biotic characteristics (soil characteristics like texture, soil humidity, soil temperature, etc.; landscape connectivity; rodent and flea species composition, climatic variables; population density in the villages and their hamlets; etc.) are collected and compared in some plague-positive and plague-negative villages in order to establish underlying ecological variables that are (partly) responsible for the presence of plague in a village.