BACKGROUND: In autoimmune haemolytic anaemia (AIHA) autoreactive antibodies directed against red blood cells are upregulated leading to erythrocyte cell death. M. suis infections in pigs (IAP) induce AIHA of both the warm and the cold type. Aim of this study was to identify target autoantigens of warm autoreactive IgG antibodies. For this, sera from experimentally M. suis infected pigs were screened for autoreactivity. RESULTS: In sera of 95 % of all tested animals actin-reactive antibodies were found. The reactivity was shown to be species specific, i.e. reactivity with porcine actin was significantly higher than with rabbit-actin. Sera of animals previously immunised with the adhesion protein MSG1 of M. suis showed reactivity with actin prior to infection with M. suis indicating molecular mimicry to be involved in specific autoreactive mechanism. A potentially cross reactive epitope could be detected. CONCLUSIONS: This is the first report of autoreactive anti-actin antibodies involved in pathogenesis of autoimmune haemolytic anaemia.