Eight type III hyperlipoproteinemic (type III HLP), homozygous E 2/2 patients were enrolled in two periods of long-term diet-gemfibrozil treatment. The combined therapy resulted in highly significant decreases in their low-density lipoprotein cholesterol, very-low density lipoprotein cholesterol, very-low density lipoprotein triglycerides, and increases in their high-density lipoprotein cholesterol during the first treatment period of 24 to 28 months. Type III HLP reasserted itself following an 8-week interruption of gemfibrozil therapy. Resumption of gemfibrozil therapy again lowered the high lipid-lipoprotein concentrations of these patients toward normal. Tuboeruptive xanthomata, palmar xanthoma, and xanthoma striata palmare subsided with treatment. Follow-up coronary arteriograms performed 2.5 to 3.0 years after initiation of diet-drug treatment showed stabilization of coronary arterial lesions, which was associated with improvement in exercise tolerance.