1. We have determined the frequency of DNA polymorphisms of the human apolipoprotein AI-CIII-AIV gene cluster, detected with XmnI, PstI, and PvuII, in a group of patients with peripheral arterial disease. 2. Of the patients, 81 had no evidence of disease in the coronary and carotid arteries, 73 had coronary artery disease but no evidence of carotid artery disease, 25 patients had carotid artery disease but no evidence of coronary artery disease, and 38 had both coronary and carotid artery disease. 3. Levels of triacylglycerol, cholesterol, apolipoprotein B and apolipoprotein AI were not significantly different between the four patient groups. 4. The frequencies of the alleles for the apolipoprotein AI-CIII-AIV polymorphisms, detected with XmnI, PstI and PvuII, did not differ significantly in the patient groups when compared with a sample of clinically well normolipidaemic individuals also from a London population. 5. All five patients with the XmnI genotype we designate X2X2 had high levels of cholesterol, apolipoprotein B and apolipoprotein AI. 6. Patients with the rare VB2 allele of the apolipoprotein CIII-AIV restriction fragment length polymorphism had lower levels of cholesterol, acylglycerol and significantly lower levels of serum apolipoprotein. 7. Our observations suggest that variation in the apolipoprotein AI-CIII-AIV gene cluster may not be contributing significantly to the development of peripheral arterial disease, but variation associated with some of the restriction fragment length polymorphisms may be involved in determining levels of cholesterol- and apolipoprotein-B-containing lipoproteins.