We have used microspectrofluorimetry with the pH-sensitive dye, BCECF, to examine the control of intracellular pH in the secretory endpieces of the sheep parotid gland. Unstimulated endpieces in HCO3(-)-free media have a cytosolic pH of 7.5 +/- 0.03 (n = 69) which is maintained by a Na(+)-dependent proton extrusion process that can be partially supported by Li+ but not by Cs+, and is not affected by changes in extracellular Cl-, HCO3- or K+. It is not blocked by SITS or DIDS, which inhibit Na(+)-(n)HCO3- co-transport and CL(-)-HCO3- exchange, nor is it sensitive to the amiloride analogs, MIA and EIPA, which inhibit Na(+)-H+ exchangers, although very high concentrations of amiloride itself (1 mmol/l) have a (probably non-specific) inhibitory effect. It seems likely that sheep parotid secretory endpieces do contain a Na(+)-H+ exchanger that drives secretion of a HCO3(-)-rich juice, and that its insensitivity to amiloride and its analogs explains why these drugs do not block fluid secretion by the intact sheep parotid gland.