Neuroleptanalgesia describes a state of sedated analgesia produced by the administration of the tranquilizer, droperidol, and the potent narcotic, fentanyl, in combination. This combination of drugs was administered intravenously to effect neuroleptanalgesia in the early treatment of eight patients with acute anterior transmural myocardial infarction. Criteria for inclusion in the study were (1) persistent ischemic pain, (2) ST segment elevation of 0.3 or more mV in at least two standard precordial leads, (3) a heart rate of 80 or more beats per minute, (4) a mean arterial pressure of 75 or more mm Hg, and (5) a cardiac index of 2.0 L/min/m2. Within 30 minutes of the administration of the drugs, all patients were relieved of pain and emotional stress. The sum of ST segment elevation from leads V1through V6(σST6) and the average ST elevation over the precordium ([unk]) decreased significantly by 57% and 56%, respectively. At the same time, there was a significant reduction in heart rate (from 112 ± 17 to 86 ± 8 beats per minute), mean arterial pressure (from 100 ± 7 to 82 ± 4 mm Hg), and pulmonary arterial wedge pressure (from 17 ± 7 to 12 ± 2 mm Hg). The cardiac index increased from 2.25 ± 0.22 to 2.40 ± 0.07 L/min/m2. Two hours later the hemodynamic parameters had returned to control levels, but the beneficial effect on myocardial injury persisted. Thus neuroleptanalgesia in the early hours of myocardial infarction can reduce preload, afterload, oxygen demand, and eventually the infarct size without depressing myocardial function.