The pathogenesis of dilated cardiomyopathy (DCM) is as yet unknown. However, it is widely believed that autoimmune mechanisms contribute to the manifestations of the disease. In sera of patients with dilated cardiomyopathy, antibodies against different antigens, including heat shock protein (hsp) 60, were found. Antibodies against other stress proteins have not yet been reported. The aim of this study, therefore, was to screen sera of patients with DCM for the presence of antibodies against the major stress proteins. Lysate of stressed human endothelial cells was used as antigenic substrate in 1- and 2-dimensional immunoblot, since this cell type has recently been shown to express the major stress proteins. Antibodies against hsp60, hsp70, and heat shock cognate protein (hsc) 70 were detected in sera of patients with dilated cardiomyopathy as compared to healthy controls. Interestingly, antibodies against hsp70 and hsc70 were found in sera of patients younger than 30 years significantly more often than in older individuals. A correlation between the presence of antibodies against stress proteins and disease activity, clinical status, or histological findings was not detected. These findings support the view that DCM might be a consequence of an infectious disease, because stress proteins are immunodominant antigens in microbial agents and antibodies against stress proteins were detected in sera of patients with infectious diseases. Whether these antibodies are of pathogenetic significance or may be used as a disease marker will have to be elucidated in future experiments.