OBJECTIVE: To show that second- or third-degree atrioventricular block occurring as an early complication of acute inferior myocardial infarction is mediated by adenosine. SETTING: Cardiac care unit. DESIGN: Uncontrolled, observational, hypothesis-driven study. PATIENTS: Patients who developed clinically significant atrioventricular nodal blockade within 4 hours of admission for acute inferior myocardial infarction. INTERVENTION: Theophylline, 100 mg/min intravenously to a maximum of 250 mg. MEASUREMENTS: Continuous multilead electrocardiographic monitoring before and after administration of theophylline. RESULTS: During a 6-month period, eight men who had had acute inferior myocardial infarction developed clinically significant atrioventricular block. Three had third-degree block, and five had high-grade second-degree block. In all patients, 1:1 atrioventricular nodal conduction was restored and normal sinus rhythm reappeared within 3 minutes of the administration of theophylline. All patients remained free of arrhythmia for at least 24 hours. CONCLUSIONS: Adenosine produced by the ischemic myocardium may induce atrioventricular nodal block. In our patients, atrioventricular nodal block was resistant to conventional therapy such as atropine, but it responded to the adenosine antagonist theophylline.