Atherosclerotic renal artery disease is an important secondary cause of hypertension. Currently, there is great interest in possible genetic determinants of cardiovascular disease. The ACE-D allele has been reported to be associated with increased risk of myocardial infarction as well as coronary re-stenosis after angioplasty. We therefore assessed whether this allele is also linked to renovascular disease by studying 56 Caucasian subjects with atherosclerotic renal artery stenosis and 74 age, sex and race matched control subjects. Genetic analysis for the ACE I/D polymorphism was performed on peripheral leukocytes using PCR techniques, including insertion-specific primers. The distribution of I and D alleles was: renal artery stenosis 8 II, 25 ID, 23 DD; and controls, 16 II, 41 ID, 17 DD. The frequency of the D allele in the renal artery stenosis group was significantly higher (D/total 71/112 = 0.66) than that of the control population [75/148 = 0.51; chi 2 = 4.17, P = 0.04; odds ratio 1.69 (95% CI 1.02 to 2.78)]. Our results suggest that the ACE-D allele may be associated with increased risk of vascular disease at sites other than the coronary circulation.