This paper presents the analyses of data obtained from eight permanent 20 km transects to determine the relative effect of local human populations and ecological factors on the distribution of large mammals within the Dzanga sector of the Dzanga-Ndoki National Park and the adjacent area of the Dzanga-Sangha Dense Forest Special Reserve in south-west Central African Republic. Principal component analysis indicated that human activities significantly influence the distribution of large mammals, even within this protected area. Distance from the village and the main road as well as the distance from secondary roads appeared to have the greatest influence. Elephants in particular were significantly less common in areas related to human use. Our study showed that poachers use roads, both primary and secondary, to penetrate into the National Park. Thus increasing anti-poaching efforts along these roads could be an effective protection measure.