Individuals with isolated low HDL cholesterol are at increased risk of coronary artery disease. It has been reported previously that this is an insulin-resistant state. We analyzed data from the 1992 Singapore National Health Survey with the objective of defining the clinical and metabolic parameters associated with isolated low HDL cholesterol. A total of 3,568 individuals were selected by stratified random sampling. Subjects with low HDL cholesterol (<0.9 mmol/l) and "ideal" total cholesterol (<5.2 mmol/l) were identified. Data on anthropometry, blood pressure (BP), insulin resistance, glucose tolerance, sex, smoking habit, and ethnic group were examined. We found that this group was heterogeneous. Those with fasting triglyceride (TG) >1.7 mmol/l (low HDL/high TG) displayed features of the insulin resistance syndrome characterized by obesity, higher diastolic BP, greater insulin resistance, and a greater tendency to have diabetes or impaired glucose tolerance (IGT). If fasting TG was <1.7 mmol/l (isolated low HDL cholesterol), individuals were similar to the general population in terms of insulin resistance and obesity. Both groups were more commonly men and Asian Indian. The ethnic difference in prevalence could not be explained by differences in diet, exercise, alcohol ingestion, or smoking. Our data support the view that Asian Indians are genetically predisposed to isolated low HDL cholesterol as well as the insulin resistance syndrome. The higher prevalence of isolated low HDL cholesterol, the young age at which individuals exhibit this phenotype (mean age 32.5 years), along with the greater propensity for Asian Indians to develop insulin resistance and IGT contribute to the threefold increased incidence of myocardial infarction in those <65 years of age in this ethnic group.