The objective of this study was to evaluate the relationship between early hemodynamic instability and myocardial ischemia and the effect of early intraveneous enalapril therapy on this relationship. In patients with myocardial infarction (MI), early treatment with angiotensin-converting enzyme inhibitors is controversial. In hypotensive patients, initiation of treatment may exacerbate myocardial ischemia and thereby affect the clinical outcome. Therefore, in the CONSENSUS II study, a total of 60 patients randomly allocated to either intravenous enalapril or placebo treatment commenced within 24 h after the onset of MI were evaluated by repeated blood pressure measurements, ambulatory ST-segment monitoring before discharge and exercise testing. Significant ST-depression was present in 34 patients. Patients with ST-depression before discharge (residual ischemia) during either exercise testing or ambulatory monitoring or both had a decrease in initial mean arterial blood pressure (MAP) of 20 vs. 9 mm Hg in those without ST-depression (n = 24), (p < 0.00001). However, patients (n = 13) with long-lasting ST-depression during Holter monitoring, ( > 60 min of ST-depression) presented with the most severe fall in MAP of 29 mm Hg (p < 0.00001) and a lower systolic blood pressure at inclusion (p < 0.01) compared to the remainder of patients. Furthermore, the number of recurrent acute ischemic events during follow-up was higher in these patients (7 vs. 1; p < 0.01). Ten of the patients treated with enalapril showed a long-lasting ST-depression versus only 3 in the placebo group (p = 0.08), and the average duration of all significant ST-depressions during Holter monitoring was significantly longer in the enalapril group compared to the placebo group (p < 0.05). Finally, 7 enalapril patients (20%) suffered an acute ischemic event in contrast to 1 patient (4%) in the placebo group (p = 0.07). In conclusion, early administration of enalapril had a potential proischemic effect in hypotension-prone patients mediated through exacerbation of the hemodynamic response, inasmuch as initial blood pressure fall after MI is related to residual myocardial ischemia and recurrent acute ischemic syndromes.