We used the Coronary Heart Disease Policy Model, a state-transition computer simulation, to assess the absolute and relative effects of two different national cholesterol interventions: a targeted program to identify and treat all individuals with elevated serum cholesterol levels (greater than or equal to 250 mg/dl) versus a populationwide program to reduce everyone's serum cholesterol level. Based on the assumptions inherent in our model, which uses the Framingham Heart Study coefficients, we estimate the targeted program would reduce projected coronary heart disease absolute incidence by 8-10% in men ages 35-54 years and by 1-4% in men ages 55-74 years. Our model suggests that similar reductions in coronary heart disease incidence could be achieved by a 10 mg/dl populationwide reduction in serum cholesterol levels. In women, the targeted program would yield greater relative and absolute benefits and would be equivalent to a approximately 23 mg/dl populationwide reduction in serum cholesterol. We conclude that it would be inadvisable to rely solely on targeted cholesterol reduction programs to reduce national coronary heart disease.