Substance P (SP) is a powerful vasodilator and this peptide is today considered to be a chemical messenger. The potential effects on circulating SP of acute changes in arterial blood-pressure was investigated in nine subjects. An increase in arterial mean blood-pressure (+33%, P less than 0.001, n = 9) was obtained by infusion of angiotensin II and a decrease in pressure (-10%, P less than 0.005, n = 6) was obtained by ganglionic blockade. The concentration of SP in plasma, from supine subjects in the normotensive condition, ranged from 3 to 13 pmol/l (with a mean of 5.6 pmol/l). SP was thus within the reference interval: 3-16 pmol/l (n.s.). Plasma SP remained very constant in each subject during the changes in blood-pressure (mean variation in plasma concentration of SP was 0.97 (SD) pmol/l). The results show that acute changes in arterial blood-pressure do not result in any detectable change in plasma SP, this seems to indicate that endogenous circulating SP has no significant role in the vascular tonus controlled by the arterial baroreflex.