Since serum cholesterol is a major component in the causal pathway of atherosclerosis, a pathological process that usually progresses with age, we have evaluated reported findings of a diminished association between serum cholesterol level and coronary heart disease in the elderly. In the Honolulu (Hawaii) Heart Program, 1480 men aged 65 years and older and free of coronary heart disease were followed up for an average of 12 years. Incidence rates of coronary heart disease increased progressively from the lowest to the highest quartile of serum cholesterol level. The independent role of serum cholesterol level as a predictor of coronary heart disease risk was evaluated with other major risk factors using a Cox multivariate regression model. The upper-lower quartile relative risk for serum cholesterol level was 1.64 (95% confidence interval, 1.14 to 2.36). The relative risk for middle-aged men was also 1.64. The results suggest that serum cholesterol level is an independent predictor of coronary heart disease, even among men older than 65 years. Thus, an elevated serum cholesterol level in the elderly should be regarded, as in middle-aged men, to be an indicator for further evaluation of lipoprotein levels and possible intervention.