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Objective-To determine whether the angiotensin converting enzyme (ACE) and the angiotensin II type 1 receptor (AT(1)R A1166C) gene polymorphism interact to increase the risk of ischaemic events, and whether this can be explained by the progression of angiographically defined coronary atherosclerosis.Design-Prospective defined substudy of the lipid lowering regression trial (REGRESS).Setting-University hospital.Patients-885 male patients with stable coronary artery disease.Main outcome measures-Incidence of ischaemic events during a two year follow up; serial quantitative coronary arteriography (mean segment diameter and minimum obstruction diameter) at baseline and after two years.Results-Patients who carried both the ACE-DD and AT,R-CC genotype had significantly more ischaemic events during the two year follow up than those carrying other genotype combinations (p = 0.035, Mantel-Haenszel test for linear association). There was no association between the two genotypes and mean segment diameter or minimum obstruction diameter at baseline or after two years.Conclusions-The suggestion that ACE-DD and AT,R-CC genotypes interact to increase the risk of ischaemic events is confirmed. However, this increased risk was not accompanied by increased progression of angiographically defined coronary atherosclerosis.