Semliki Reserve comprises the Semliki Wildlife Reserve, Semliki Controlled Hunting Area (CHA) and an adjacent area of wetland extending to Lake Albert, whose shores have swamps with Miscanthus and papyrus Cyperus papyrus. It borders the Rift Valley escarpment that rises to 1,500 m on the eastern boundary. The Rwenzori foothills are to the south and the CHA adjoins the Wildlife Reserve in the north-west, along the border with Democratic Republic of Congo. These reserves are generally flat, lying at the bottom of the Rift Valley. Two rivers, Wasa and Mugidi, and their tributaries drain the Wildlife Reserve into Lake Albert and the River Semliki marks the western border of the CHA. The local microclimate (influenced by the surrounding topography) and past human activities within the reserves have created a mosaic of vegetation-types, including lake-shore flats and swamps, grassland, wooded grassland, bush grassland, woodland, swamp and riverine forest.
The species-richness is relatively high, with a list of 350 bird species for the Wildlife Reserve. The birds in the two reserves are mainly savanna-woodland species, with water-associated species along various streams through the reserves as well as at the shores of the lake. The tall vegetation along the marshy shores of the lake is home to Balaeniceps rex and other wetland birds, such as Microparra capensis and Nettapus auritus, whilst the papyrus swamp along the rivers holds Laniarius mufumbiri and perhaps other papyrus specialists. Although this site does not qualify for the Sudan–Guinea Savanna biome, it holds six species of this biome, including several that are at the extreme south of their range (but which are common in the Wildlife Reserve), such as Ptilostomus afer, Merops bulocki and Lamprotornis purpureus. Sixteen species of the Guinea–Congo Forests biome also occur in the Wildlife Reserve, as do four species of the Lake Victoria Basin biome.
In the 1960s, the reserve was renowned for its high populations of Kobus kob and Panthera leo, but these were reduced to low levels through poaching during the period 1971–1986, as were Loxodonta africana and Alcelaphus buselaphus. An unknown number of chimpanzees Pan troglodytes occur in the reserve along the riverine forests.

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