Infusion of adenosine (0.022-2.2 mg/min) into the left anterior descending (LAD) coronary artery of 26 patients produced a dose-dependent increase in blood pressure without a change in heart rate. At adenosine 2.2 mg/min, systolic pressure rose by 21.0 +/- 2.2 mmHg from 134 +/- 4.3 mmHg (P less than 0.001) and diastolic pressure increased by 10.4 +/- 1.1 mmHg from 76 +/- 1.9 mmHg (P less than 0.001). The rise in arterial pressure was associated with a 22 +/- 3.4% increase in systemic vascular resistance (P less than 0.01) and no change in cardiac output (-2.8 +/- 4.3%, P = NS). Plasma norepinephrine levels rose by 40 +/- 14% from 105 +/- 9 pg/ml (P less than 0.05) and epinephrine levels by 119 +/- 31% from 37 +/- 9 pg/ml (P less than 0.01). Right atrial infusion of adenosine produced insignificant hemodynamic effects, suggesting that systemic spillover of adenosine was not responsible for the observed effects. In 20 cardiac transplant patients with denervated hearts, LAD infusion of adenosine (2.2 mg/min) produced no change in systolic pressure (-0.1 +/- 1.6 mmHg from 139 +/- 3.4 mmHg, P = NS) and a decrement in diastolic pressure (-4.7 +/- 1.2 mmHg from 98 +/- 2.5 mmHg, P less than 0.01). Thus, infusion of adenosine into the LAD coronary artery causes a reflex increase in arterial pressure due to a rise in systemic vascular resistance, probably as a result of increased sympathetic discharge. This reflex pathway may be of importance in disease states such as myocardial ischemia, in which myocardial adenosine levels are elevated.