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Abstract: The social and behavioral sciences are at a crossroads in public health. In this paper, we attempt to describe a path toward the further integration of the natural and behavioral sciences with respect to the study of behavior and health. Three innovations are proposed. First, we extend and modify the “stream of causation” metaphor along two axes: time, and levels of nested systems of social and biological organization. Second, we address the question of whether ‘upstream’ features of social context are causes of disease, fundamental or otherwise. Finally, we propose the concept of a risk regulator to advance the study of behavior and health in populations. To illustrate the potential of these innovations, we develop a multilevel framework for the study of health behaviors and obesity in social and biological context. [Copyright &y& Elsevier]