Correlations of low-density lipoprotein (LDL) predominant particle diameters (PPD) were investigated in samples taken from the San Antonio Family Heart Study. A frequency histogram showed LDL PPD occurs in at least two distinct modes, at about 25.5 and 26.9 nm, with the nadir at about 26.2 nm. Triglyceride (TG) concentrations were strongly correlated with LDL PPD, accounting for nearly 50% of the variation. However, examination of the relationship between TG concentrations and LDL PPD showed considerable overlap of the two LDL size categories for samples having intermediate levels of TG (1-3 mmol/l). In order to examine the factors associated with particle size variation within this region of overlap, 163 pairs of samples, which contrasted peak particle diameters, were matched for TG concentrations and for sex and age. In this matched set, LDL-related measures (i.e. LDL-C, apoB, apoE, and TG concentrations) did not differ. However, several high-density lipoprotein (HDL) measures were significantly related to the LDL particle size category. This category predicted a substantial proportion of variation in HDL-C (9.7%) and apoAI (7.5%) concentrations, and in HDL size distributions of cholesterol (13.6%) and apoAI (10.3%). Other traits related to insulin resistance syndrome (IRS) (glucose and insulin concentrations, blood pressure, and adiposity measures) were tested for association with the LDL size category. None of these traits were related to LDL size after adjusting for TG, except fasting and postchallenge glucose concentrations which showed modest correlations (P-values were 0.02 and 0.05, respectively). The data suggest that in addition to the strong effects of TG, there is also an aspect of LDL particle size variation that is strongly associated with variation in HDL concentration and particle size distribution, perhaps reflecting common metabolic determinants of lipoprotein size.