Cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) was examined in a community-based sample of 599 genetically unrelated school-aged children (5-17 years) and their parents. Risk factors used as components of Syndrome X included hyperinsulinemia, obesity, dyslipidemia and high blood pressure defined by values above the age-, sex- and race-specific 75th percentiles of fasting insulin, body mass index, triglycerides/high-density lipoprotein cholesterol ratio and mean arterial pressure, respectively. Based on observed to expected ratio there was an excess of parents (father and/or mother) and their offspring with clusters of three or four disorders (P < 0.05-0.001). In contrast, the number of parents and offspring with two disorders was significantly lower than expected by chance alone (P < 0.05-0.01). Based on paternal, maternal, and parental Syndrome X, the odds ratios (95% confidence interval) for offspring having the same cluster were 7.2 (1.9-27.2), 8.6 (3.1-23.6) and 7.9 (3.5-18.1), respectively. In terms of individual risk factors of parents used as predictors, adverse levels of their insulin and BMI significantly increased the risk of offspring having Syndrome X (P < 0.01-0.001), whereas the effect of parental insulin was considerably reduced after parental BMI was adjusted for. In contrast, parental dyslipidemia and high blood pressure were not associated with the occurrence of Syndrome X in their offspring. These results confirm the familial nature of Syndrome X and suggest that conditions of obesity and the attendant hyperinsulinemia in parents may underlie this familial association.