The present report analyzes the prevalence of the cluster of metabolic abnormalities defined as syndrome X (high blood glucose, high blood pressure, low high density lipoprotein (HDL) cholesterol, and high triglycerides) and its impact on cardiovascular disease mortality in a large cohort of men and women (22,561 men and 18,495 women). These individuals were participants in a series of epidemiologic investigations of cardiovascular disease conducted in Italy between 1978 and 1987. They were followed for an average of 7 years, during which time a total of 1,218 deaths occurred (1,003 in men and 215 in women). Deaths were coded according to the International Classification of Diseases, 9th Revision (ICD-9). The prevalence of the full cluster of metabolic abnormalities (syndrome X) was low in the population as a whole, with only 3.0 percent of men and 3.4 percent of women exhibiting the full cluster of abnormalities that comprise syndrome X. The risk of death from all causes and cardiovascular disease increased with increased numbers of metabolic abnormalities in both men and women. Mortality from cancer was significantly increased in women (but not in men) with syndrome X, compared with women with no metabolic abnormalities. Population attributable risks for all cause mortality and cardiovascular disease mortality were 0.06 and 0.09 in men and 0.04 and 0.48 in women when assessed by population cutpoints. These data from a large population-based epidemiologic investigation indicate that the presence of a full cluster of metabolic abnormalities from syndrome X is an important risk factor for cardiovascular disease and all-cause mortality in both men and women, but that the low prevalence of such a cluster in the population reduces the public health impact of syndrome X. The majority of individuals who die from cardiovascular disease present elevations in any one, two, or three of the metabolic abnormalities. The notion of the cluster of metabolic abnormalities (syndrome X) should not distract our attention from established individual risk factors that have been proven to be major causes of cardiovascular disease death and disability in our society.