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In the 1980s, behavioral variations across geographically and socially defined populations were the central focus of AIDS research, and behavior change was seen as the primary means of controlling HIV epidemics. Today, biological mechanisms—especially other sexually transmitted infections, antiretroviral therapy, and male circumcision—predominate in HIV epidemiology and prevention. We describe several reasons for this shift in emphasis. Although the shift is understandable, we argue for a sustained focus on behavioral mechanisms in HIV research in order to realize the theoretical promise of interventions targeting the biological aspects of HIV risk. We also provide evidence to suggest that large reductions in HIV prevalence may be accomplished by small changes in behavior. Moreover, we contend that behavioral mechanisms will find their proper place in HIV epidemiology and prevention only when investigators adopt a conceptual model that treats prevalence as a determinant as well as an outcome of behavior and that explicitly recognizes the dynamic interdependence between behavior and other epidemiological and demographic parameters.