The present study aimed to examine the association between low density lipoprotein (LDL) particle size and glucose and insulin variables and with other risk factors that have been related to insulin resistance syndrome. LDL particle size was determined in two groups of subjects who participated in the first examination of the Jerusalem Diabetes Study and who were invited to be re-examined after 8-10 years. The first group were non-diabetic subjects who were found to have at the first examination high insulin levels (above the sex and age specific 90th percentile of the 2 h post-glucose load insulin distribution). The second group was a random sample of individuals who had normal insulin and glucose levels at baseline. Sex-, Age- and body mass index (BMI) mean adjusted LDL-cholesterol (C), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) levels were significantly different among the LDL subclass groups. Fasting glucose levels and hemoglobin A(1c) did not differ statistically by LDL subclasses. Fasting and 2-h post load insulin levels were significantly higher in persons with LDL subclasses III and IV (small LDL), intermediate in those with LDL subclass II, and lowest in those with LDL subclass I (large LDL). Insulin resistance had an effect on the association between lipids, lipoproteins and LDL particle size. Multivariate analyses indicated that LDL-C, HDL-C and TG were independently associated with LDL particle size variability. The addition of 'insulin resistance' or insulin and glucose levels had no independent effects on LDL particle size. In conclusion, an association of LDL particle size with the cluster of risk factors that characterize the insulin resistance syndrome has been demonstrated. The association of 'insulin resistance' and LDL particle diameter, however, is not mediated directly through the level of insulinemia but via alterations in lipid metabolism.