The relationship between dietary lipids and the 16-year incidence of coronary heart disease (CHD) morbidity and mortality was examined in two male cohorts, aged 45 to 55 years (n = 420) and 56 to 65 years (n = 393) from the Framingham Study. Dietary lipids were assessed through a single 24-hour recall at the initiation of follow-up in 1966 to 1969. In the younger cohort, there were significant positive associations between the incidence of CHD and the proportion of dietary energy intake from total fat and monounsaturated fatty acids. The proportion of energy intake from saturated fatty acids had a marginally significant positive association with CHD. The associations remained even after adjustment for cardiovascular disease risk factors, including serum cholesterol level, suggesting that their effects are at least partially independent of other established risk factors. In contrast to the younger cohort, none of the dietary lipids were associated with CHD in the older cohort. Dietary intervention for the prevention of CHD in younger men is supported by these findings.