Streptokinase (SK) is a routinely used thrombolytic agent but it is immunogenic and allergenic; staphylokinase (STA) is a potential alternative agent which is under early clinical evaluation. The comparative prevalence of antibodies against recombinant STA (STAR) and against SK was studied in healthy subjects and their induction with intravenous administration in small groups of patients. Enzyme-linked immunosorbent assays, using microtiter plates coated with STAR or SK and calibration with affinospecific human antibodies, revealed 2.1 to 65 micrograms/ml (median 11 micrograms/ml) anti-STAR antibodies and 0.9 to 370 micrograms/ml (median 18 micrograms/ml) anti-SK antibodies (p < 0.001 vs anti-STAR antibodies) in plasma from 100 blood donors, with corresponding values of 0.6 to 100 micrograms/ml (median 7.1 micrograms/ml) and 0.4 to 120 micrograms/ml (median 7.3 micrograms/ml), respectively, in 104 patients with angina pectoris. Three out of 17 patients with Staphylococcus aureus bacteremia had significantly increased anti-STAR antibody levels (150, 75 and 75 micrograms/ml), and STAR neutralizing activities (2.2, 3.6 and 4.1 micrograms STAR neutralized per ml plasma, respectively). In 6 patients with acute myocardial infarction, given 10 mg STAR intravenously over 30 min, median anti-STAR antibody levels were 3.5 micrograms/ml at baseline, 2.9 micrograms/ml at 6 to 8 days and 1.2 mg/ml at 2 to 9 weeks, with median corresponding titers of STAR neutralizing activity at 2 to 9 weeks of 42 micrograms/ml plasma. Conversely, in 5 patients treated with 1,500,000 units SK over 60 min, median anti-SK antibodies increased from 2.9 micrograms/ml at baseline to 360 micrograms/ml at 5 to 10 days, with corresponding median SK neutralizing activities of 13 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)