The main fractions obtained by ultracentrifugal separation of normal human serum lipoproteins form distinct classes. On the high-density side (d > 1.063) HDL1, HDL2, and HDL3; on the low-density side: LDL1, LDL2, and chylomicra are represented by particles of increasing density, lipid content, and diameter, the latter ranging from about 100 Å (HDL3) to about 15.000 Å (largest chylomicron).Distinctions between classes are evidenced by the action of solvents, the analysis of the N-terminal amino acids of peptides and immunochemical and metabolic properties.High-density lipoproteins (HDL) and low-density lipoproteins (LDL) form distinct groups displaying dissimilarities on the basis of many criteria. There can be little doubt that the origin, structure, and functions of the two groups are different. Among the LDL, LDL2, and LDL1 are both very similar and complex, LDL2 appearing to be a precursor of LDL1. HDL on the other hand may be partially derived from the chylomicra as a result of intravascular lipoprotein action upon some of these transient, very low-density lipoproteins with which they share characteristic peptides.Since no satisfactory structural model for the lipoproteins has yet been published, it was the purpose of this paper to re-examine all pertinent data and to present new speculations regarding these structures.It could be demonstrated that the lipoproteins on the low-density side are particles characterized by a protein coverage which is uniform over their extensive dimensional range and which corresponds to 36 A2 per amino acid residue. LDL1, the smallest of the group and the most abundant of the normal human serum lipoproteins, appears to consist of a single monolayer of lipids bearing adsorbed protein and surrounding a central core of occluded water. The general configuration of the adsorbed protein is still unknown. It is demonstrated that our present knowledge of the configuration of protein and synthetic polypeptide monolayers, most of which is derived from experiments with the film balance at air–water and petroleum ether – water (so-called oil–water) interface, cannot apply to these lipoproteins since there exists a considerable difference in physical and ionic topography between the experimental "oil–water" interface and the interface involved in lipoproteins.Part of the demonstration consists of the structural analysis of the lipid molecules involved. Diagrams representing these molecules, which are exact as to interatomic distances and bond angles are presented and used to explain the important phenomenon of sterol–phospholipid association. The latter is expected to play a considerable role in LDL1 (and presumably in the external lipid layer of LDL2 and chylomicra) where phospholipids and cholesterol (free and bound) represent 90% of the total molecular species with cholesterol (free and bound) accounting for two-thirds of them. By virtue of their associative properties, such molecules must exist in organized arrays conferring a directive influence to the lipid film on the configuration of the adsorbed protein. This should be quite different from the dispersive action of the disorganized petroleum ether layer in the so-called "oil–water" interface which induces partial random uncoiling of the protein chains.A demonstration of the method used in studying lipoprotein films by the use of diagrams is given. Its application to the cholesterol monolayer yielded for the limiting area a value in excellent agreement with that obtained with the film balance.