In addition to well-established roles in the management of stable angina, unstable angina and heart failure, nitrates are widely used in the management of acute infarction and the subacute period of recovery after infarction. A meta-analysis suggested that intravenous nitrate therapy in acute infarction reduced mortality by 35%. Subsequently, two recently reported 'mega' trials, GISSI-3 and ISIS-4, addressed the role of nitrates during and after infarction. The results of the mega trials have failed to substantiate a statistically significant benefit for nitrates. The contrast between the promising results of the meta-analysis and the disappointing results of the mega trials raises a number of issues considered in this paper. The role of nitrates in acute myocardial infarction remains unclear. The mega trials do offer some suggestive evidence of an early benefit of nitrate therapy. If any benefit does exist, it must be much smaller than the 35% reduction in mortality suggested by the meta-analysis. Further trials are required to assess the possibility of an early acute benefit. Any benefits will probably apply only to subgroups of infarcts.