Background: Adult calcific aortic stenosis is a well-known clinical entity but its pathophysiology and cellular mechanism have yet to be defined. Objectives: To determine whether there is an association between the presence and severity of adult calcific aortic stenosis and Chlamydia pneumoniae seropositivity. Methods: Forty adult patients (23 women, 17 men) were divided into three groups according to echocardiographic aortic valve area: Group A-7 symptomatic subjects (age 67 +/- 7 years) with normal aortic valve and normal coronary angiogram, Group B - 16 patients (age 73 +/- 6) with moderate ACAS (AVA > 0.8 <= 1.5 cm(2)), and Group C - 17 patients (age 76 +/- 7) with severe ACAS (AVA <= 0.8 cm(2)). We tested for immunoglobulins M, G and A as retrospective evidence of C. pneumoniae infection using the micro-immunofluorescence method. Past C. pneumoniae infection was defined by IgG titer > 16 <= 512. Results: No patients in group A showed positive Ig for C. pneumoniae. IgM was not detected in any of the patients with ACAS (groups B and C) while 2 of 17 patients (12%) in group C showed IgA for the pathogen. High titers of IgG were found in 14 of 33 (42%) of the patients with moderate or severe ACAS: 5 of 16 (31%) in group B and 9 of 17 (53%) in group C (P = 0.2). Both groups had the same prevalence of coronary artery disease (66%). AVA was lower in, IgG-seropositive patients than in the seronegative group (0.88 +/- 0.3 cm vs. 1.22 +/- 0.4 cm(2), respectively, P = 0.02). Conclusions: Past C. pneumoniae infection may be associated with a higher prevalence and greater severity of ACAS.