Adenosine acts at many sites to modulate neuronal activity. The purpose of this study was to investigate a possible role for adenosine as a neuromodnlator of brainstem cardiovascular control. Microinjections of adenosine (0–2.3 nmol) were made stereotaxically into various brainstem sites. Injection of adenosine into the nucleus tractus solitarii (NTS) produced dose-related decreases in heart rate and systolic and diastolic blood pressures. Maximal changes occurred 90 seconds after injection. Injection into the area postrema also produced decreased heart rate and systolic and diastolic blood pressures. No significant effect occurred following injection into the Cl area. Adenosine 5-triphosphate and its analogue, β,γ-methylene adenosine 5′-triphosphate also produced doserelated and potent vasodepressor and bradycardia effects in the NTS. Injection of l,3-dipropyl-8-psulfophenylxanthine (0.92 nmol), a potent adenosine receptor antagonist, produced no effect itself, but abolished for 45 minutes the actions of further injections of adenosine and adenosine 5′-triphosphate (but not L-glutamate) in both the NTS and area postrema. Thus, NTS and area postrema injections of adenosine decrease blood pressure and heart rate in anesthetized normotensive rats through adenosine receptors located in these areas. These findings support a role for endogenous adenosine as a central modulator in cardiovascular control.