The historical time of acute symptom onset is not always an accurate indication of the timing of onset of an acute myocardial infarction (AMI). Consideration of electrocardiographic (ECG) timing parameters could supplement historical timing alone as a clinical guide for decisions regarding the use of reperfusion therapy. Three hundred ninety-five patients from 4 trials of thrombolytic therapy conducted in the northwestern United States and western Canada are included in the present study. A total of 316 patients received either streptokinase or tissue plasminogen activator, and 79 received no reperfusion therapy. Historical time of symptom onset was acquired by emergency or cardiology department personnel and recorded on patient report forms. An ECG method for estimating the timing of the AMI, the Anderson-Wilkins (AW) acuteness score, was calculated from the initial standard 12-lead recording by investigators blinded to the knowledge of symptom duration or any other study variables. Tomographic thallium-201 imaging 7 weeks after hospital admission was used to measure final AMI size. The ECG timing method achieved a relation with final AMI size similar to that previously reported for historical timing. The AW acuteness score proved most useful for anterior AMI location when there was a > or = 2 hour delay following symptom onset, but was most useful for the inferior AMI location when there was a < 2 hour delay. Despite a longer delay, patients with high AW acuteness scores had 50% lower final anterior AMI size than those with low scores; and despite a shorter delay, those with low ECG acuteness scores had 50% greater final inferior AMI size than those with high scores. The AW acuteness score combined with the historical estimation of symptom duration should provide a more accurate basis for predicting the potential for limitation of final AMI size than either method alone. These results could potentially provide the basis for developing a new method for noninvasive guidance of clinical decisions regarding administration of reperfusion therapy in the initial evaluation of patients with AMI.