1. Changes in extracellular pH (pHo) are known to produce large effects on vascular tone, but the mechanisms involved are not understood. As changes in intracellular pH (pHi) can also affect vascular tone, we have investigated the effects of changing pHo upon both pHi and tone. 2. Strips of rat mesenteric resistance vessels were loaded with the pH-sensitive fluorophore SNARF 1; thus tension and pHi could be simultaneously measured as pHo was altered. 3. Whenever pHo was altered there was a corresponding alteration of pHi. Furthermore, when pHo was changed the pHi change was more rapid than that reported to occur in other cells. The time to half-peak intracellular response was 38 +/- 4 s (n = 11). The induced pHi change was also less attenuated than in many other cells studied. Thus a ratio of 0.73 was obtained for the change in pHi per unit pHo change (n = 7). 4. An increase in pHi produced by an increase in pHo was accompanied by an increase in tension in the vascular strips. In other experiments pHi was increased at constant pHo by the addition of the weak base trimethylamine (40 mM). This also elevated tension in the strips. Conversely when pHo was changed while pHi was held at resting values, no change in vascular tone occurred. 5. It is concluded that the effects of pHo on vascular tone are due to the induced change in intracellular pH, and that the vascular smooth muscle cell is functionally well adapted to respond to changes in tissue pH, thereby allowing blood flow to a tissue to be rapidly altered to meet changing needs.