To test the hypothesis that chronic infection with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus is associated with coronary heart disease risk in elderly men, a nested case-control study in a cohort investigated in 1985 and 1990 in the town of Zutphen, The Netherlands, was designed. Fifty-four cases with a first diagnosed coronary event between 1985 and 1990, and 108 age-matched control subjects free of coronary heart disease during follow up were included in the study. The overall prevalence of antibodies to cytomegalovirus was 74.7%, to H. pylori 75.9% and to C. pneumoniae 84.0%. A high level of antibodies to C. pneumoniae was associated with an increased coronary heart disease risk (OR = 2.76; 95% CI = 1.31-5.81). This association was stronger in cases developing both myocardial infarction and angina pectoris, than in cases developing only one of these. This association was independent of potential confounders. Antibodies to cytomegalovirus or H. pylori were not associated with coronary heart disease risk. These results support the hypothesis of a role of chronic C. pneumoniae infections in the immunopathogenesis of atherosclerosis.