The insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease (CHD) risk factors, including low high-density lipoprotein cholesterol (HDL-C) levels, obesity and increases in triglyceride (TG), blood pressure, small low-density lipoprotein particles (LDL), and both fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified 3 uncorrelated factors that explained 66% of the variance among these variables, based on data from women participating in examination 2 of the Kaiser Permanente Women Twins Study in Oakland, CA during 1989-1990. The factors were interpreted as: 1) body mass/fat distribution, 2) insulin/glucose, and 3) lipids: TG, HDL-C, LDL peak particle diameter. In this analysis, heritability of each of the factors was estimated based on data from 140 monozygotic and 96 dizygotic pairs of non-diabetic women twins. Heritability estimates were calculated using the classical approach, the analysis of variance (ANOVA) approach, and the maximum likelihood approach. For the body mass/fat distribution factor heritability estimates suggest moderate genetic influences; 0.61 (P < 0.001), 0.14 (P > 0.05), and 0.71 (P < 0.001), respectively. The insulin/glucose factor appeared to be highly heritable, with estimates of 0.87, 0.92, and 0.57 (all P < 0.001), respectively. The heritability estimates for the lipid factor were moderate and consistent across methods: 0.25 (P < 0.10), 0.32 (P < 0.05), and 0.30 (P < 0.05), respectively. These results are consistent with genetic influences on each of the 3 "factors," and suggest that both genetic and environmental effects are involved in the clustering of IRS risk factors.