Throughout the Second World War a central component of the Franklin D. Roosevelt administration’s post-war planning was an attempt to win the support of Great Britain for a multilateral economic system, based on the internationalist principles of free and equal access to the world’s markets and resources. This paper explores the impact on Anglo-American economic diplomacy of a faction within the Roosevelt administration, defined as ‘hemisphere isolationists’. United by a preoccupation with Latin American affairs, alongside an instinctive disdain for the European powers, this group pursued policies which had the effect of excluding British interests from Latin America for the post-war era. As such, they represented a regionalist challenge to broader internationalist conceptions of the post-war world.