High performance gel chromatography (HPGC) was used to separate lipoproteins on the basis of their size and to generate lipoprotein profiles for plasma collected from patients with different lipoprotein phenotypes. These profiles provided a direct measurement of low density lipoprotein (LDL)-cholesterol which was more precise than LDL-cholesterol values calculated by the Friedewald equation. In addition, LDL-cholesterol concentrations were obtained in patients with combined hyperlipidemia in whom LDL-cholesterol could not be accurately calculated by the Friedewald equation. The response of LDL-cholesterol to the drug gemfibrozil was reliably monitored and in addition changes in LDL particle size could be assessed from the LDL apolipoprotein B/cholesterol ratio. HPGC also assisted in the diagnosis of type III hyperlipidemia by revealing a characteristic lipoprotein profile. HPGC-derived lipoprotein profiles provided additional useful clinical information for combined hyperlipidemia (Fredrickson lipoprotein phenotypes IIb, III).