The pH has marked effects on the blood flow in several vascular beds but the underlying mechanisms remain incompletely understood. It is still not agreed, for example, whether it is the fall in extracellular pH or intracellular pH that is responsible for changes in tone resulting from hypercapnic acidosis. The issue has been further complicated by the recent discovery that nitric oxide (NO) may also be involved in vasodilator responses to hypercapnia with the result that, in some laboratories, attention has been focused away from vascular smooth muscle. The recent availability of fluorescent dyes sensitive to pH has enabled some of the uncertainties in this field to be addressed. In light of these new observations, we have attempted to put older viewpoints in perspective. We conclude that, whilst a fall in smooth muscle intracellular pH is likely to be responsible for immediate responses to acidosis, the extracellular pH probably plays the predominant role in the steady state. The role of NO is best investigated in the cerebral circulation where it plays an important modulating role in the response to acidosis, and is probably of extravascular origin.