BACKGROUND The objective of this study was to examine specific membrane binding of [125I]-acylation stimulating protein (ASP) in cultured human skin fibroblasts obtained from normal subjects and patients with hyperapoB. ASP is a small basic protein isolated from human plasma that stimulates triglyceride synthesis (TGS) and glucose transport (GT) in human skin fibroblasts and adipocytes. METHODS In the present study, three groups were studied: normal (NASP-NB) subjects, hyperapoB subjects with normal plasma ASP (NASP-HB) and hyperapoB subjects with high plasma ASP (HASP-HB). RESULTS ASP-induced TGS in fibroblasts from HASP-HB subjects was significantly less than in the two control groups with normal plasma ASP (NASP-NB and NASP-HB). Similarly, ASP stimulation of GT was less in HASP-HB fibroblasts than in the NASP-HB fibroblasts or the NASP-NB subjects. Insulin-induced TGS was similar in all three groups as was insulin-stimulated GT. As well, protein kinase C-mediated stimulation was equivalent among the three groups both for GT and for TGS. There was no significant difference in the binding affinity (Kd) of [125I]-ASP to intact cells in any group. By contrast, binding of [125I]-ASP revealed a significantly lower Bmax of the HASP-HB cell lines than the NASP-NB cells and the NASP-HB cells. CONCLUSIONS A decrease in the ASP cell-surface receptor concentration is responsible for decreased ASP stimulation of TGS, and GT and may contribute to the inefficient postprandial triglyceride (TG) clearance in HASP-HB subjects.