The value of thrombolytic therapy in myocardial infarction is well established, while any beneficial effect of adjunct therapy is more uncertain. In a double-blind, randomized, parallel-group study the effect of combined intravenous infusions of streptokinase and isosorbide dinitrate (ISDN) on enzyme-estimated infarct size was investigated. One hundred consecutive patients with strong clinical and electrocardiographic suspicion of myocardial infarction, admitted to the coronary care unit within 8 hours after the onset of symptoms, were given a streptokinase infusion of 1.5 million units for 1 hour and a titrated dose of ISDN or placebo for 48 hours. From isoenzyme B of creatine kinase (CK-B) values measured every 4 hours, the infarct size was calculated and the possible presence of reperfusion was evaluated. The infarct size in patients receiving ISDN infusion was reduced (p = 0.04, one-sided test) compared with placebo. By subdividing the patients according to whether or not reperfusion had occurred, the infarct size appeared to be similar following ISDN and placebo in patients with reperfusion (419 versus 369 U/L), whereas the infarct size in patients not reperfused was markedly reduced after treatment with ISDN (223 versus 1320 U/L, p = 0.003). In conclusion, the present study demonstrates that the infarct size may be reduced by other means than reperfusion and it supports the use of combined infusion of thrombolytic agents and nitrates in patients with suspected myocardial infarction.