Cholesteryl ester transfer protein activity may have a physiological effect on high-density lipoprotein levels. We examined restriction fragment length polymorphism associated with the cholesteryl ester transfer protein gene and the apolipoprotein AI gene in a group of 60 unrelated subjects selected from an initial survey of 5000 subjects on the basis of their high-density lipoprotein levels being high or low at the extremes of the distribution. The activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol acyltransferase, EC 220.127.116.11) were also determined. Analysis by selection of those with a low high-density lipoprotein cholesterol level (��� 1.1 for males, ��� 1.2 for females) gave 32 individuals with 24% B2 alleles. Selection of subjects with a high-density lipoprotein cholesterol level (��� 2 mmol/l) gave 17 with 62% B2 alleles. The group with low levels of high-density lipoprotein cholesterol had higher activity of cholesteryl ester transfer protein and significantly elevated triacylglycerol levels when compared with the group with high levels of high-density lipoprotein cholesterol. A further significant finding was the correlation of the MspI restriction fragment length polymorphism detected by the apoliprotein AI gene with lecithin:cholesterol acyltransferase activity.