Cryo-electron microscopy was used to analyze the structure of low density lipoprotein from normolipidemic subjects (N-LDL), phospholipid-depleted N-LDL (PD-LDL), small dense LDL from hypertriglyceridemic subjects (SD-LDL), and reconstituted discoidal high density lipoproteins (rHDL). In different projections of N-LDL, a high density component of the particle was visible as two parallel bands or as a single ring. Projections of PD-LDL were very similar to those of N-LDL, indicating that the contribution of phospholipid headgroups to the observed high density structure is minor. In preparations of SD-LDL, projections with two high density bands or a single high density ring were rare. Instead, triangular and diamond-shaped projections were recognized. In different projections of discoidal rHDL, a high density component was visible as a single band or as a single ring. The present results indicate that cryo-electron microscopy reveals the distribution of apolipoproteins within lipoprotein particles. Thus, apolipoprotein B-100 (apoB) in N-LDL appears to be organized as a double ring around the particle, while apoB in SD-LDL is indicated to have a different conformation. Cryo-electron micrographs of rHDL are consistent with the presence of apolipoprotein A-I on the periphery of the lipoprotein disc.