OBJECTIVE--To investigate the clinical significance of reciprocal ST depression on the presenting electrocardiogram in patients with acute myocardial infarction treated by thrombolysis. DESIGN--A prospective cohort analytical study. SETTING--A London district general hospital. SUBJECTS--Two hundred and fifty eight consecutive patients with acute myocardial infarction treated with thrombolysis. INTERVENTIONS--All patients underwent treadmill stress testing after a mean (SEM) of 10 (3) days; 200 patients (78%) were referred for coronary arteriography at 30 (16) days. MAIN OUTCOME MEASURES--Relation between reciprocal ST depression at presentation and several endpoints: time from start of chest pain to hospital presentation, electrocardiographic changes during early treadmill stress testing, presence of multivessel coronary disease, and clinical outcome in terms of recurrent ischaemic events (death, reinfarction, and unstable angina) during a 10 (range six to 12) month follow up. RESULTS--Presentation was generally early, but in this group of patients reciprocal ST depression was significantly related to the time from the start of symptoms, those with reciprocal change presenting on average one hour earlier than those without. Although reciprocal change on the presenting electrocardiogram was weakly associated with ST depression on treadmill stress testing, it was not indicative of remote ischaemia as a result of multivessel coronary disease or high grade collateralisation of the infarct related artery. There was no association between reciprocal change and the incidence of recurrent ischaemic events. CONCLUSION--Reciprocal ST depression on the presenting electrocardiogram seems to be a benign electrical phenomenon related to the time from the start of symptoms. It does not necessarily predict an adverse prognosis in patients treated by thrombolysis.