A general method is proposed for estimating the potential impact of a prevention program involving risk factor modification on the incidence of specific diseases in a target population. An evaluative framework for comparing alternative intervention strategies is also presented. On the basis of results from epidemiologic studies, the user must specify certain parameters regarding the distribution of the risk factor that is to be modified in the population, the magnitude of the association between the risk factor and disease, and the total risk of disease in the population. A quantitative measure, called the potential impact fraction, is derived to estimate the proportion of expected new cases that may be prevented under intervention programs of varying success. Estimates of this measure are then used to assess the potential efficacy, effectiveness, adequacy, and efficiency of planned intervention strategies. The method is illustrated with published data relating relative weight and coronary heart disease among middle-aged U.S. men, comparing different strategies of weight reduction. Key assumptions of the method and interpretation of results are discussed.