A genetic analysis of atherosclerotic patients as well as healthy subjects using an apoA-I gene specific probe confirmed that an EcoRI restriction fragment length polymorphism is related to the development of atherosclerosis. Three subjects with severe coronary heart disease were found to be homozygous for a 6.5 kb fragment hybridizing to the apoA-I probe. In the atherosclerotic patient group 44% were heterozygous for this fragment, compared to 9.5% in the control group. The distribution of genotypes in the atherosclerotic and control groups was significantly different. Among the heterozygous subjects, specific differences were found after digestion of their DNA with Bam HI restriction endonuclease.