We randomized 352 patients with pain suggestive of acute myocardial infarction who were seen less than 3 h after onset of symptoms to either tissue plasminogen activator or placebo. The impact of treatment on chest pain score was assessed during the first 24 h and related to limitation of final myocardial damage as assessed by various indirect markers. The most marked effect of tissue plasminogen activator was observed in the chest pain score being reduced by 43% in the tissue plasminogen activator group as compared with placebo. Limitation of infarct size with tissue plasminogen activator reached the following percentage values when various methods were used: maximum serum lactate dehydrogenase I activity, 32%; vectorcardiography (QRS vector difference), 20%; electrocardiography (Palmeri score), 20%; ejection fraction, 9%. We conclude that early thrombolysis in acute myocardial infarction reduces the severity of chest pain by nearly 50%. The effect on chest pain is much more marked as compared with the effect on various markers of the final ischemic damage.