Recent studies have demonstrated that cytomegalovirus (CMV) DNA was found in atherosclerotic coronary arteries in restenotic lesions, and prior infection with CMV could be a strong independent risk factor for restenosis after coronary atherectomy. We studied the correlation between anti-CMV antibody titer and coronary artery disease. Sixty-five patients (50 men and 15 women) with coronary artery disease were enrolled prospectively. All had symptomatic coronary artery disease with an angiographic documentation of a de novo single coronary lesion. All underwent balloon coronary angioplasty and were followed for 12 months with a thallium perfusion scan 3 months after angioplasty. Patients who had recurrent chest pain and/or a positive thallium scan had another coronary angiography. Blood samples were taken before angiography and 1 and 3 months later. Patients with high anti-CMV titer ≤1:800 had a higher prevalence of coronary artery disease (p <0.001) than seropositive patients with a lower antibody titer (≤1: 400); patients with high antibody titer (≤1:800) had a higher restenosis, rate than seropositive patients with a low antibody titer (≤1:400) (p <0.05). High antibody titers against CMV (IgG) may be a strong marker for coronary artery disease, and might predict post-coronary angioplasty restenosis. These findings support the infectious theory of atherosclerosis (especially with prior CMV infection), and also suggest that a chronic immunologic response has a role in atherosclerosis and restenosis.