Heat shock proteins (HSPs) are a group of highly conserved proteins that show extensive homology at the DNA and protein level among bacterial and mammalian species. Furthermore, bacterial HSPs induce specific cellular and humoral immune responses in mammals. Cross-reacting antibodies may therefore be induced in chronic infections. Recently, it has been claimed that patients with arteriosclerosis (AS) of the carotid arteries have significantly elevated antibody titers to mycobacterial HSPs. In this study, we extended the spectrum of vascular diseases and analyzed sera from patients with systemic vasculitis and systemic lupus erythematosus (SLE) for the presence of anti-HSP antibodies. Anti-HSP antibodies, tested in an ELISA with recombinant mycobacterial HSP 65, were significantly elevated in patients with vasculitis (n = 56; p < 0.01) and AS (n = 29; p < 0.0001), but only marginally in patients with SLE (n = 22; p > 0.05) compared to healthy controls (n = 90). These findings further support the concept of infection-induced immune reactions playing a pathogenic role in the development of both AS and vasculitis.