The medullary raphe nuclei are involved in central autonomic regulation. In all species investigated, electrical stimulation of the raphe nuclei causes cardiovascular responses, although, these changes vary between species. The present study was designed to investigate the participation of these nuclei in cardiovascular regulation in the guinea pig. We studied the effects on arterial blood pressure (BP) and heart rate (HR) of electrical stimulation (isolated cathodal square wave pulses for 10 s at 100 Hz, 40-100 microA and 1-ms pulse duration) within the medullary raphe nuclei in urethane-anesthetized (1.2 g/kg, i.p.) guinea pigs (400-600 g, either sex). Electrical stimulation of the same sites was performed on a group of paralyzed (Flaxedil, 1 mg/kg, i.v.) and artificially ventilated animals. Stimulation sites were histologically defined and maps of the stimuli were obtained for the effect of electrical stimulation on arterial blood pressure. In another series of experiments L-glutamate (0.2 M) was microinjected (75 to 150 nl) into the nucleus raphe obscurus. Electrical stimulation of the raphe nuclei produced predominantly pressor responses (delta = +15 to +100 mmHg; 43% of the stimulated sites). Hypotension (delta = -10 to -25 mmHg, 24% of the stimulated sites), biphasic responses (2%) or no change in BP (31%) were evoked from fewer stimulation sites. Pressor responses were also predominant in paralyzed animals (delta = +15 to +95 mmHg; 47% of the stimulated sites), and after microinjection of L-glutamate into the raphe obscurus (A = +20 to +45 mmHg). The present results demonstrate that in the guinea pig the stimulation of these nuclei evokes mainly pressor responses. These responses are similar to those obtained in the rat and hamster but opposite to those observed in the cat and rabbit.