High Quality Content by WIKIPEDIA articles! Interstate 66 (I-66) is an Interstate Highway in the eastern United States. As indicated by its even route number, it runs in an east–west direction. Its western terminus is at Middletown, Virginia, at an intersection with Interstate 81; its eastern terminus is in Washington, D.C., at an intersection with U.S. Route 29. Interstate 66 has no physical or historical connection to U.S. Route 66.