Elevated levels of homocyst(e)ine and infection by Chlamydia pneumoniae have been hypothesized individually to play a role in coronary artery disease (CAD), but the mechanisms are unclear. Data on a possible association are not available. We investigated the correlation between IgG antibody titers against C. pneumoniae and fasting plasma homocyst(e)ine in 234 consecutive male patients with CAD. Chlamydial antibodies to a recombinant genus-specific lipopolysaccharide (LPS) were measured with ELISA. Total homocyst(e)ine (tHcy) concentrations were measured by high-performance liquid chromatography (HPLC). Thirty-seven subjects were classified hyperhomocyst(e)inemic (fasting homocyst(e)ine>14 micromol/l, group A), and 197 subjects were below cut-off (tHcy<14 micromol/l, group B). Prevalence of IgG seropositivity against C. pneumoniae was significantly higher in group A (68%) as compared to group B (39%, P=0.002). Antibody titers were also significantly higher in hyperhomocyst(e)inemic subjects than in cases with low homocyst(e)ine levels (P=0.002). Overall titers correlated significantly with tHcy levels (r(2)=0.222, P=0.001). Hyperhomocyst(e)inemia was associated with arterial hypertension (P=0.003), intake of lipid lowering drugs (P=0.022) and quite not with low folate concentration (P=0.052). No association was seen for IgG seropositivity or homocyst(e)ine and age, body mass index, smoking, diabetes, vitamin B(6) and B(12), cholesterol and triglycerides. These data indicate an association between elevated plasma homocyst(e)ine concentrations and chlamydial IgG antibody titers in patients with CAD.