Streptokinase (SK), a nonenzymatic protein produced by group C beta haemolytic streptococci, is a potent antigen. It is used worldwide as a thrombolytic agent in the treatment of acute myocardial infarction (AMI). Specific antiheart antibodies (AHA) have been found with a significantly high incidence in patients with AMI, and after streptococcal infection as a result of stimulation by constituents of the group A streptococci antigenically cross-reactive with sarcolemmal portion of the muscle fiber of the heart. Since there may be partial antigenic identity of group C streptococcal membranes with membranes isolated from group A streptococci, we have designed a prospective study to evaluate the incidence of serum AHA (and of other organ-specific and non-organ-specific antibodies) in 36 patients with AMI, 14 of whom treated with SK. AHA, of IgG class, were of the sarcolemmal-subsarcolemmal type, and did not fix complement. They were found in 4/36 patients already on admission; of the 32 patients negative, none developed AHA later, on days 7, 15 and 21 of hospitalization, also after treatment with SK (in 14 cases). There was no significant difference either within or between the two SK-treated and non-SK-treated groups also with regard to the incidence of organ-specific and non-organ-specific autoantibodies. These findings do suggest that the intravenous SK therapy does not facilitate the formation of AHA in AMI.