The syndrome of Henoch-Schoenlein purpura developed in a 74-year-old woman after receiving streptokinase as thrombolytic therapy for an acute myocardial infarction. Renal biopsy revealed mesangial hypercellularity with deposits of IgA. Skin biopsy also revealed IgA deposition. Immunological studies showed evidence of sensitization to streptokinase. Elevated IgG, IgA, IgM, and IgE antistreptokinase antibodies were detected in the acute serum. Positive immediate skin reactivity to streptokinase was also present. Serum precipitins to streptokinase disappeared when IgA was removed from the serum. Positive staining with biotinylated streptokinase was seen in the skin in the same pattern of distribution as IgA. These findings strongly support the role of streptokinase and IgA in the pathogenesis of Henoch-Schoenlein purpura in this patient. A control group of streptococcal-infected patients showed no immune response to streptokinase. Another control group of streptokinase-treated patients, who had no untoward reaction, had elevated immunoglobulin classes and precipitins to streptokinase. However, the precipitating antibody was IgG and streptokinase skin tests were negative.