In the 1940s, the Secretaría de Salubridad y Asistencia (SSA- Secretariat of Health and Welfare) hoped to unify Mexico to eliminate smallpox from within its borders. In 1952, Mexico had achieved that goal, but the year marked a significant shift in their smallpox campaigns. A unified front broke down as a focus on national elimination shifted to an international emphasis on disease prevention and control across borders after 1952. International and local interests competed for the SSA’s attention. This thesis argues that smallpox vaccination no longer acted as a centralizing force after 1952. Instead, conflicting goals encouraged national and international disputes which slowed efforts to centralize Mexico’s federal government in the 1950s and 1960s. That challenge to centralization after 1952 contradicts existing scholarship that sees the Ruiz Cortines and López Matos administrations as the apex of the central, dominant PRIísta state.