Social-ecological (SE) models are becoming more widely used in health behavior research. Applying SE models to the design of interventions is challenging because models must be tailor-made for each behavior and population, other theories need to be integrated into multi-level frameworks, and empirical research to guide model development is limited. The purpose of the present paper is to describe a SE framework that guided the intervention and measurement plans for a specific study. The trial of activity for adolescent girls (TAAG) is a multi-center study of interventions to reduce the decline of physical activity in adolescent girls. The TAAG framework incorporates operant learning theory, social cognitive theory, organizational change theory and the diffusion of innovation model in a multi-level model. The explicit and practical model developed for TAAG has already benefited the study and may have elements that can generalize to other health promotion studies.