The aim of this study was to examine relationships between low density lipoprotein (LDL) metabolism, in vitro binding, and particle size. Twenty four study subjects, 17 men and 7 women, had elevated plasma total cholesterol (TC), ranging from 174 to 232 mg/dl, and LDL cholesterol (LDLC) ranging from 113 to 195 mg/dl after 12 weeks on a Step I diet. The fractional clearance rate (FCR) for LDL ranged from 0.233 to 0.619 pools/day (0.366 +/- 0.021) and was significantly correlated with plasma triglycerides (TG) (P < 0.05). Although there was no relation between FCR and binding in the study group as a whole, those subjects with an FCR within the normal range (< 0.45, n = 20), showed a significant negative correlation between FCR and the KD for LDL binding, (r = 0.52). A subset of four subjects with an elevated FCR (> 0.45) had higher production rate (PR) (P < 0.005) and a significant positive correlation between the KD for LDL binding and FCR (P < 0.05). LDL size varied from 240.0 to 265.8 A and was significantly inversely correlated with plasma TG (P < 0.001) but there was no relation between LDL size and metabolism or binding affinity. Thus, there appears to be a correlation between binding affinity and clearance for subjects who had normal LDL production and clearance rates. On the other hand, mechanisms other than binding affinity appear to influence clearance in subjects with elevated rates of production and clearance.