Low density lipoproteins (LDLs) were isolated by ultracentrifugation and radiolabeled with '"In. The in vitro binding of these radiolabels onto platelets of normolipemic volunteers (n = 15) and patients (n=36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites capable of binding 1,757±289 ng protein of '"In-LDL per 10′ platelets (dissociation constant [ATd], 6±3figprotein/mL) in healthy volunteers and significantly (p<0.001) lower amounts in the FH patients (mean, 633±341 ng protein/109platelets;Kd, 10±5figprotein/mL). The capacity of native LDL to displace bound '"In-LDL by half amounted to 10±4figprotein/mL in volunteers and 22±8figprotein/mL in FH patients (p<0.001). Treatment with gemflbrozil alone or in combination with cholestyramine in 10 patients resulted in increased "'In-LDL binding by platelets (470±307 [mean±SD] ng protein/109platelets before therapy, 948±650 ng protein/10 after 2 months of therapy [p<0.01], and l,272±701 ng protein/109platelets after 6 months of therapy [p<0.01]). Significant correlations between nl In-LDL binding capacity and apolipoprotein B (r=−0.83,p<0.001) and LDL cholesterol (r=&#151; 0.80,p<0.000) concentrations were found. Patients with clinically manifested atherosclerosis (p<0.01) and those with diabetes mellitus (p<0.05) had significantly lower platelet LDL binding sites. The findings demonstrate "'In-lipoprotein-specific binding sites on human platelets. Platelets of patients with heterozygous FH express lower numbers of binding sites, which could be upregulated during lipid-lowering intervention. It is concluded that high-affinity LDL binding may involve in vivo processes related to platelet activation in hyperlipemic disorders.