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In both its 1995 decision United States v. Lopez and in its 2000 decision United States v. Morrison, the Supreme Court had adopted a narrow economic interpretation of congressional authority to regulate intrastate activities under the Commerce Clause. In four separate cases, three circuit courts (the District of Columbia, Fourth, and Fifth Circuits) struggled with deciding whether Congress may still protect endangered and threatened species that have little commercial value under the Commerce Clause after Lopez and Morrison. In each case, the court concluded that Congress did have the authority to protect endangered species under the Commerce Clause, including small isolated intrastate species, although there were dissenting opinions in each case. Because Lopez and Morrison failed to provide an adequate framework for analyzing Congress's authority under the Commerce Clause, the four decisions applied different and sometimes clearly contradictory rationales to justify regulation of endangered species under the Commerce Clause.

In 2005, however, the Court in Gonzales v. Raich limited the scope of Lopez and Morrison by allowing Congress greater latitude to regulate intrastate activities under the Commerce Clause if they are regulated as part of a comprehensive statutory scheme that on the whole appropriately regulates interstate commerce. By emphasizing the authority of Congress to regulate non-economic, intrastate activities as part of a comprehensive scheme of regulation, both the Raich majority opinion and Justice Scalia's concurring opinion- with its emphasis on the Necessary and Proper Clause-support the view that Congress has authority under the Commerce Clause to regulate all endangered species, including intrastate species or those with no direct commercial value in interstate commerce, because the ESA's comprehensive scheme is necessary to preserve interdependent species and ecosystems that do have significant impacts on interstate commerce. Furthermore, because the statute regulates only endangered and threatened species, leaves all other species to state regulation, and promotes concurrent federal-state regulation of wildlife, the ESA's regulation of endangered species is cabined by the type of limiting principles that Justice Scalia applied in his Raich concurrence, and, therefore, the ESA is consistent with the Constitution's federalist values.