Until 1972, Uganda's national parks boasted of large numbers of large mammal species. Following the breakdown of law and order between 1972 and 1985, large-scale poaching led to an unprecedented decline in numbers of most large mammals in Uganda's national parks. However, the extent of decline varied in the different parks across different animal species. We have investigated the genetic effects of these reductions in four mammalian species (the common warthog, African savannah elephant, savannah buffalo and common river hippopotamus) from the three major parks of Uganda using both microsatellite loci (for elephant and warthog populations) and mitochondrial control sequence variation in the warthogs, elephants, buffaloes and hippopotamuses. Queen Elizabeth National Park showed extreme reduction in nucleotide diversity for two species, the common warthog (π = 0.0%) and African elephant (π = 0.4%); no such decrease was found for the two other species, the buffalo (π = 3.7-5.4%) and hippopotamus (π = 1.7-1.9%), in the three parks. Nuclear microsatellite markers on the other hand showed high gene diversity in all populations in the common warthog (mean He 0.66-0.78) and the African savannah elephant (mean He 0.68-0.72). We interpret these results in terms of varying poaching pressure in the different parks, susceptibility of different species to poaching and differences in effective population sizes at the mitochondrial and nuclear loci.