Is it domestic politics or the international system that more decisively influences foreign policy? This article focuses on Latin America's three largest powers to identify patterns and compare outcomes in their relations with the regional hegemon, the United States. Through a statistical analysis of voting behavior in the UN General Assembly, we examine systemic variables (both realist and liberal) and domestic variables (institutional, ideological, and bureaucratic) to determine their relative weights between 1946 and 2008. The study includes 4,900 votes, the tabulation of 1,500 ministers according to their ideological persuasion, all annual trade entries, and an assessment of the political strength of presidents, cabinets, and parties per year. The findings show that while Argentina's voting behavior has been determined mostly by domestic factors and Mexico's by realist systemic ones, Brazil's has a more complex blend of determinants, but also with a prevalence of realist systemic variables.