To determine if plasma lipoproteins interact and therefore possibly regulate intestinal lipoprotein metabolism, we investigated the binding, internalization, and degradation of 125I-labeled low density lipoprotein (LDL) and high density lipoprotein (HDL) by enzyme-dispersed rat intestinal mucosal cells. Both human and rat LDL and HDL were bound, internalized, and degraded in a concentration-dependent manner with calculated half-saturation occurring at approximately 30, 35, 35, and 15 micrograms/ml for human LDL, rat LDL, human HDL, and rat HDL, respectively. Isolated brush border membranes had no saturable or specific binding sites for 125I-labeled HDL or LDL, suggesting that lipoproteins may be bound to receptors on lateral or basal membranes of mucosal cells. Compared with HDL, LDL binding was characterized by a large non-specific component. LDL of human and the rat were not only displaced by excess LDL but at least as effectively by excess HDL of their own species. Labeled HDL was displaced by corresponding unlabeled lipoproteins, but human LDL could produce only minor displacement of human HDL3. ApoE-deficient rat HDL, separated by heparin-Sepharose affinity chromatography also showed highly specific saturable binding to intestinal cells. Thus, apparently two different lipoprotein binding sites exist in intestinal plasma membranes, one recognizing B and/or E apoproteins present in human and rat LDL and rat HDL while another binds human HDL3 and apoE-deficient rat HDL which contain A apoproteins as major components.