The aim of the study was to prove the long-lasting and continuously harmful effect of chronic Chlamydia pneumoniae (CPn) infection on vessel walls in patients with diffuse coronary artery disease (CAD). In surgically obtained endarterectomized atherosclerotic plaques grade VI-VIII (Stary classification) from 10 patients with diffuse coronary artery disease and chronic (7) or past (3) CPn infection, signs of inflammatory response of the vessel wall on infectious agents were studied. In all 10 endarterectomized plaque step serial sections, immunologic signs of vessel wall response were present (positive T- and B-lymphocytes, macrophages, and capillarogenesis). In 8 of 10 patients' atherosclerotic plaque, unique features of active vasculitis in the neoarteriolar wall as well as arteriologenesis, were found. Seven of these 8 patients had serologically proven chronic CPn infection, and 1 had past infection. Features of vasculitis as well as arteriologenesis were absent in 2 patients who recovered from CPn infection at the time of surgery. In the endarterectomized segments of 3 randomly chosen patients in this study, the polymerase chain reaction method revealed positive DNA of CPn. Two of these patients had chronic infection, but the third had only a past CPn infection. This study provides evidence that CPn infection has continuous and a long-lasting inflammatory response in the high-grade atherosclerotic coronary artery vessel wall.