The fundamental aim of the International Studies of Infarct Survival (ISIS) collaborative group is to assess reliably the balance of any benefits and risks for widely practicable treatments that might produce moderate but worthwhile mortality reductions in patients with suspected acute myocardial infarction. Substantial numbers of lives might be saved by such treatments, but benefits of the size that can realistically be expected may be reliably detected only by randomized trials involving some tens of thousands of patients. In order to recruit such numbers, ISIS involves almost no extra work for collaborators: hence, busy general hospitals--where the majority of acute myocardial infarction patients are actually treated--can take part easily. The ability of the ISIS trials to yield clear, reliable answers depends entirely on the collaboration of many doctors and nurses in the participating hospitals. For this reason, publication of the final results is in the names of all the collaborators. All patients, high risk as well as low risk, presenting within 24 hours of the onset of suspected acute myocardial infarction are eligible for ISIS-4, provided that the responsible physician does not initially consider there to be any clear indications for, or clear contraindications to, any one of the trial treatments--nitrate, angiotensin-converting enzyme inhibitor, or magnesium. Patients are randomized between 1 month of oral controlled-release mononitrate or placebo; between 1 month of oral captopril or placebo; and between 24 hours of intravenous magnesium or open control (i.e., no infusion). (Patients who are to be given intravenous or other non-trial nitrate for just a few days can still be entered). In this trial, 3 quite different treatments will each be evaluated. At first glance, this may appear to complicate the results, but in fact appropriate statistical analysis of this "factorial" design will allow all patients to contribute fully to assessment of the separate effects of each treatment (while also providing important information about the combined effects). Apart from giving the trial treatments, all other aspects of individual patient management are left entirely to the responsible physician to decide. For example, previous trials in suspected acute myocardial infarction have shown that, for many categories of patients, antiplatelet and fibrinolytic therapy can save lives. Hence, most collaborating doctors will wish to give antiplatelet therapy routinely and to start fibrinolytic therapy in many of their patients before randomizing them in ISIS-4.(ABSTRACT TRUNCATED AT 400 WORDS)