Over the past centuries the native caribou of West Greenland has gone through extensive population size fluctuations, with reductions as great as 90% in less than 20 years. Norwegian semi-domestic reindeer were introduced to the Nuuk area in 1952 because of the small number of caribou in Greenland. Although the reindeer and caribou were initially kept separated, mixing has occurred since the 1970's. We investigated the genotypic structure of caribou and reindeer in South-west Greenland, using five polymorphic microsatellite markers isolated from cattle, sheep, goat and red deer. A total of ninety samples were collected, which included samples from caribou of four different regions and samples from two different reindeer herds. Based on the genetic variation of the five markers, our results shows that the caribou and the reindeer populations in the six regions sampled are genetically differentiated within each group and the two subspecies are differentiated from each other. A likely explanation for the genetic isolation of the populations investigated is that natural barriers (glaciers and wide fjords) exists in the area. Furthermore we found that introduced Norwegian domestic reindeer hybridized with the native Greenlandic caribou in two areas neighbouring Nuuk.