Coronary heart disease (CHD) remains the leading cause of mortality in the U.S. Innovations in reperfusion therapies can potentially reduce CHD morbidity and mortality associated with acute myocardial infarction (AMI) when treatment is initiated within the first few hours of symptom onset. However, delay in seeking treatment for AMI is unacceptably lengthy, resulting in most patients being ineligible for reperfusion therapies. The Rapid Early Action for Coronary Treatment (REACT) Trial is a four-year, 20-community, randomized trial to design and test the effectiveness of a multi-component intervention to reduce patient delay for hospital care-seeking for AMI symptoms. This manuscript describes the development and content of the theoretically-based REACT intervention and summarizes: (1) the research literature used to inform the intervention; (2) the behavioral theories used to guide the development, implementation, and evaluation of the intervention; (3) the formative research undertaken to understand better decision-making processes as well as barriers and facilitators to seeking medical care as perceived by AMI patients, their families, and medical professionals; (4) the intervention design issues that were addressed; (5) the synthesis of data sources in developing the core message content; (6) the conceptualization for determining the intervention target audiences and associated intervention components and strategies, their integration with guiding theoretical approaches and implementation theories for the study, and a description of major intervention materials developed to implement the intervention; and (7) the focus of the outcome, impact, and process measurement based on the intervention components and theories on which they were developed.