This study investigated neuronal, blood pressure, and heart rate responses to adenosine microinjection into caudal and rostral NTS of anesthetized rats. The site of recording and microinjection was verified chemically by observing the responses to a test dose of l-glutamate (5 nmol) and histologically at the conclusion of the experiment. Neuronal firing rate increased (+29.4 +/- 5.3%) and decreased (-48 +/- 9.4%) in response to l-glutamate microinjection into the rostral and caudal NTS, respectively. These opposite neuronal responses were followed by depressor (-32.4 +/- 8.3 vs. -36 +/- 5.5 mmHg) and bradycardic (-25.2 +/- 7.7 vs. -25.8 +/- 3.4 beats/min) responses to l-glutamate microinjection into the two subareas of the NTS. Microinjection of a submaximal dose (1 nmol) of adenosine into the NTS produced site-dependent cardiovascular responses which were preceded by similar inhibition of neuronal firing (-60 +/- 4 vs. -55.9 +/- 1.7%). Whereas adenosine microinjection into the rostral NTS elicited modest pressor (+10.1 +/- 2.1 mmHg) and tachycardic (+9 +/- 3.9 beats/min) responses, its microinjection into the caudal NTS produced depressor (-29.2 +/- 5.3 mmHg) and bradycardic (-14.6 +/- 1.7 beats/min) responses. These findings suggest that compared to l-glutamate, adenosine produces opposite (rostral) and similar (caudal) neuronal and cardiovascular effects in the two subareas of the NTS. In the caudal NTS, adenosine (0.1, 1, and 10 nmol) elicited dose-related inhibitory neuronal and cardiovascular responses that were attenuated by systemic theophylline but not 8-(p-sulfophenyl) theophylline (8-SPT) administration. The neuronal and cardiovascular responses to adenosine microinjection into the caudal NTS were also attenuated by microinjection of 8-SPT into the same area. Finally, single-unit activity inhibited by adenosine or l-glutamate microinjection into the caudal NTS was also inhibited by baroreceptor loading and excited by baroreceptor unloading. These findings suggest a) l-glutamate elicits opposite neuronal responses in the rostral and caudal NTS; b) the distinct hemodynamic responses elicited by adenosine in the two subareas may be related, at least in part, to their differing responses to l-glutamate; and c) the similarity between the neuronal responses to adenosine and l-glutamate microinjection into the caudal NTS and the response of the same neurons to baroreceptor activation support the hypothesis that adenosine plays a neuromodulatory role in the processing of baroreceptor information.