The prevalence of cardiovascular disease (CVD) and atherosclerosis varies among several minority ethnic groups in the United States. Recently, small, dense low density lipoprotein (LDL) particle size has been recognized as a risk factor for CVD. We examined LDL size as a possible explanation for differences in CVD rates in 1571 subjects from the Insulin Resistance Atherosclerosis Study (IRAS), a multiethnic study of insulin resistance and cardiovascular risk factors. LDL size (A) was significantly different by ethnic group (African Americans 262.1+/-0.6, Hispanics 257.6+/-0.6, and non-Hispanic whites 259.2+/-0.4, P<0.001). Ethnic differences in LDL size continued to be statistically significant after adjustment for upper body adiposity, insulin resistance, and glucose tolerance status. However, after further adjustment for other cardiovascular risk factors, especially ethnic differences in triglyceride and high density lipoprotein (HDL) cholesterol levels, the ethnic differences in LDL size were markedly attenuated and in general no longer statistically significant. The relation of triglyceride, HDL cholesterol, insulin resistance, and adiposity to LDL size in each ethnic group was similar. LDL size differs by ethnic group, which is independent of obesity or insulin resistance. These ethnic differences appear to be due to ethnic variations in dyslipidemia (especially differences in triglyceride levels); ethnic differences in LDL size are not consistent with previously reported ethnic dissimilarities in CVD or atherosclerosis.