Human plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) were radioiodinated and their interaction with washed human platelets was assessed. Both ligands were bound by the platelet at 37 degrees C, and an apparent equilibrium was attained within two hours. Minimal binding was observed at 22 degrees C or 4 degrees C. The specificity of these interactions was indicated by the observations that: (a) labeled and nonlabeled lipoproteins interacted with the platelet with the same apparent affinity; (b) nonlabeled lipoproteins inhibited binding, whereas unrelated plasma proteins did not; and (c) the platelet-bound ligands exhibited the appropriate apoprotein chain compositions when analyzed by polyacrylamide gel electrophoresis. Binding of HDL and LDL was found to be independent of the state of platelet activation and did not require divalent ions. Binding of HDL to the platelet was saturable, and a class of sites that maximally bound 1,585 +/- 390 HDL particles, with a dissociation constant of 3.1 X 10(-8) mol/L, was identified. Binding of LDL to the platelet was more complex, but evidence for a class of sites that bound 7,075 +/- 4,800 LDL particles, with a dissociation constant of 4 X 10(-8) mol/L, was found. LDL was a poor inhibitor of 125I-HDL binding to the platelet, whereas HDL was an effective inhibitor of 125I-LDL binding. The capacity of HDL to bind or inhibit LDL binding was not dependent on its apoprotein E content. These results are most readily interpreted in terms of two types of lipoprotein interaction sites on platelets: (1) an HDL binding site that does not bind or interacts poorly with LDL, and (2) an LDL binding site that recognizes or is otherwise altered by HDL. The HDL site may be similar to the HDL receptor expressed by steroidogenic tissues in terms of apoprotein specificity. The LDL site is not the same as the LDL receptor of most extrahepatic cells.