The 8,501-acre Two Rivers National Wildlife Refuge is one of five refuges in the Mark Twain National Wildlife Refuge Complex. Formerly known as the Brussels District of Mark Twain Refuge, most of Two Rivers Refuge is located near the confluence of the Illinois and Mississippi rivers. The refuge is comprised of five divisions: Apple Creek, Batchtown, Calhoun, Gilbert Lake, and Portage Island.

The refuge is managed for migratory birds, endangered species, and migratory fish. Management techniques mimic the historic flood cycle of the rivers to support native plant and animal communities characteristic of large river ecosystems. The refuge provides an important link in the chain of resting, feeding, and wintering areas for migratory species using the Mississippi Flyway, as well as important habitat for many resident wildlife species.

The Mark Twain Refuge Complex was established in 1958. General Plan lands were purchased by the U.S. Army Corps of Engineers as part of their project to maintain a nine-foot-deep navigation channel in the Mississippi River. Lands excess to the project came under U.S. Fish and Wildlife Service management through a cooperative agreement in 1963. Since then, the Service has purchased additional acreage.

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