The purpose of our study was to identify the central nervous system site(s) of action of capsaicin responsible for producing changes in cardiovascular function. To do this, capsaicin was administered into several cerebroventricular regions of chloralose-anesthetized cats while monitoring arterial blood pressure and heart rate. Administration of capsaicin (1, 3, 10, 30, 100 and 300 micrograms) into the forebrain ventricles with restriction of the drug to these ventricles resulted in no significant changes in arterial pressure or heart rate. In contrast, administration of capsaicin into either the 4th ventricle or the cisterna magna resulted in significant increases in arterial pressure and heart rate. Intravenous administration of these doses produced no consistent effects on these indices of cardiovascular function. Bilateral application of capsaicin (3 ng/side) to a ventral medullary site, i.e., Schlaefke's area, known to be a sensitive site for drug-induced cardiovascular responses, resulted in striking increases in pressure and heart rate. Microinjection of this agent into the nucleus tractus solitarius, however, failed to evoke any changes in pressure and heart rate. These results indicate that the area on the ventral surface of the medulla is extraordinarily sensitive to capsaicin and may serve as the site of capsaicin-induced changes in cardiovascular function.