The cardiovascular effects of adenosine-induced controlled hypotension were studied in 10 patients undergoing cerebral aneurysm surgery. Adenosine and its metabolites were measured in arterial plasma using high-pressure liquid chromatography. Whole body and cerebral arteriovenous oxygen content differences (AVDO2), arterial lactate levels, and arteriojugular lactate differences were determined. In order to reduce the dose requirement of adenosine, the patients were pretreated with the adenosine uptake inhibitor, dipyridamole (0.3–0.4 mg · kg-1). During the infusion of adenosine (0.14 ± 0.04 mg · kg-1· min-1) the mean arterial blood pressure decreased by 43%, from 82 to 46 mmHg, during a mean hypotensive period of 32 min, without signs of tachyphylaxis. The arterial adenosine level increased from 0.15 ± 0.02 to 2.45 ± 0.65 μM (P< 0.01). Hypotension was caused by a profound decrease in peripheral vascular resistance (61 ± 3%,P< 0.01), which was accompanied by an increase in cardiac output (44 ± 9%,P< 0.01). Heart rate increased moderately by 16 ± 5% (P< 0.01). Pulmonary vascular resistance and central venous pressures were unaffected. Arterial lactate and PaO2were unchanged, while whole body oxygen consumption was decreased by 13 ± 4% (P< 0.05). The AVDO2across the brain was decreased by 37 ± 5% (P< 0.05) without signs of lactate formation. The authors conclude that adenosine rapidly induces a stable and easily controlled hypotension in humans by dilation of arterial resistance vasculature.