With the United States entry into World War II, the 181st was relieved from the 26th Division and assigned to the Eastern Defense Command (EDC) on 27 January 1942. (The 181st Infantry was replaced as part of the 26th Division by the 328th Infantry Regiment). The 211th Field Artillery Battalion (105 mm howitzers) was attached to form a regimental combat team. The 181st Infantry was assigned to the EDC conducting coastal patrols from Higgins Beach, Maine to Watch Hill, RI to prevent the landing of German agents from U-Boats. From May 1942 through November 1943 the 3rd Battalion HQ with companies I and M were posted at the South Hingham Camp, along with B company, 132nd Combat Engineer Battalion, while Company L and Battery B, 211th Field Artillery Battalion were at the Ipswich Camp. Company K of the 181st and Battery D of the 211th FA were at the Plymouth Camp. The regimental headquarters and other units were at Camp Framingham. The 181st Infantry moved to Fort Dix, NJ on 5 December 1943 and was deactivated on 8 February 1944; the soldiers were sent to Italy as infantry replacements in the 3rd, 34th and 36th Infantry Divisions.