Objective—To evaluate the feasibility for Rift Valley fever virus (RVFV) to enter the continental United States by various routes as well as to identify states in which domestic and wild ruminant and human populations would be most vulnerable to exposure to RVFV.

Study Design—Pathways analysis.

Sample Population—Animals, commodities, and humans transported from RVFV-endemic countries to the continental United States between 2000 and 2005.

Procedures—Initially, agent, host, and environmental factors important in the epidemiologic aspects of RVFV were used to develop a list of potential pathways for release of RVFV into the continental United States. Next, the feasibility of each pathway was evaluated by use of data contained in governmental and public domain sources. Finally, entry points into the continental United States for each feasible pathway were used to identify the domestic and wild ruminant and human populations at risk for exposure to RVFV.

Results—Feasible pathways for entry of RVFV into the continental United States were importation of RVFV-infected animals, entry of RVFV-infected people, mechanical transport of RVFV-infected insect vectors, and smuggling of live virus.

Conclusions and Clinical Relevance—Domestic ruminant livestock, ruminant wildlife, and people in 14 states (Alabama, California, Florida, Georgia, Maine, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, South Carolina, Texas, and Virginia) appeared to be most vulnerable to exposure to RVFV. Pathways analysis can provide the requisite information needed to construct an effective targeted surveillance plan for RVFV to enable rapid detection and response by animal health and public health officials.