OBJECTIVE: To evaluate the benefit to risk ratio of thrombolytic treatment in patients with small inferior acute myocardial infarction (AMI). Controlled studies relating the benefit from thrombolysis with initial electrocardiographic features are scarce and of limited sample size. DESIGN: Retrospective study of 728 patients with a first inferior AMI of six hours' duration from the Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study comparing streptokinase with placebo stratified by the initial sum ST segment elevation (sigma ST) of 0.8 mV or less and greater than 0.8 mV, and 636 patients from the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial comparing double blind streptokinase with reteplase stratified by either sigma ST or the presence of precordial ST segment depression. RESULTS: ISAM study patients with an sigma ST of greater than 0.8 mV had a significant mortality benefit from streptokinase throughout six years, while those with an sigma ST of 0.8 mV or less showed a trend to higher mortality at six months (6.3% streptokinase v 5.1% placebo). Despite significantly smaller infarcts and fewer clinical complications in patients with an sigma ST of 0.8 mV or less (ISAM and INJECT) or the absence of precordial ST segment depression (INJECT) thrombolytic treatment was associated with higher early mortality than in those with initially larger ST segment deviations. CONCLUSION: Thrombolytic treatment in patients with inferior AMI presenting with larger ST segment deviations is associated with improved survival throughout six years. The risk to benefit ratio, however, in terms of early mortality in patients who have an sigma ST of 0.8 mV or less and no precordial ST segment depression may be unfavourable.