We examined the relationship between the risk of CVD mortality and morbidity and HCT over a period of 34 years of follow-up in the 5209 men and women in the Framingham cohort. There was an increased risk of all-cause death as well as morbidity and mortality due to CVD in subjects with HCT values in the highest quintile. There was no evidence of a decreased risk of CVD in men with lower than median HCT values, and women actually showed increased risk of CVD events with lower HCT values, indicating a J- or U-shaped relationship between HCT and CVD events. The impact of HCT on CVD events appears to differ for different age groups and by sex. HCT is significantly related to the incidence of CVD, including CHD, MI, angina pectoris, stroke, and IC in younger men. In younger women, HCT is related to the incidence of CVD, CHD, MI, and mortality from CVD and CHD. A negative association with CHF incidence and stroke death is noted in elderly women. These results support the hypothesis that HCT is an important risk factor for some CVD events, an association that merits further investigation.