Wide fluctuations of both urinary pH and the partial pressure of CO2 (PCO2) occur in normal physiological circumstances and in a variety of pathological conditions. However, the effect of extracellular pH on the contractility of human ureteric muscle has not been clearly defined. This study has established, using a microsuperfusion technique, that an increased superfusate PCO2 increases the magnitude of the phasic contraction to electrical field stimulation. A similar extracellular acidosis induced by alteration of the [HCO3-], at constant [Na+] and free [Ca2+], was without significant effect. Furthermore, when both superfusate PCO2 and [HCO3-] were simultaneously increased at constant pH the contractile response was similar to that when PCO2 alone was raised. These observations suggest that the changes of tension were mediated by intracellular pH changes, providing it is assumed that the ureteric smooth muscle cell membrane is permeable to CO2 but impermeable to H+ and HCO3-. The occurrence of an increase of force in the presence of an acidosis is a highly significant and unusual finding, since it has been assumed that the classical association between acidosis and negative inotropy, seen in cardiac muscle, was also applicable to smooth muscle.