Based on six years of follow-up evaluations of the Framingham, Mass, men and women aged 49 to 82 years, it was found that a low-density lipoprotein (LDL) cholesterol concentration was associated with a low incidence of coronary heart disease (CHD) risk but with a statistically significant excess of stroke incidence in women and of deaths from non-CHD causes in both sexes. There was no suggestion that an elevated HDL cholesterol level was associated with an excess incidence of any of the cardiovascular end points considered or of death. An inverse relation of high-density lipoprotein (HDL) cholesterol level with CHD and its major consequences, CHD death and congestive heart failure, was observed. Triglyceride determinations seem to add little information respecting cardiovascular risk to that elicited from HDL and LDL cholesterol and other known cardiovascular risk factors. While the relation of HDL and LDL cholesterol with CHD is paralleled by findings from a variety of sources, the inverse relation of LDL cholesterol with stroke in women and with death from non-CHD causes requires additional confirmation and exploration.