Calcitonin is known to stimulate Ca2+ reabsorption and natriuresis and to increase adenosine 3',5'-cyclic monophosphate levels in early distal tubule, but its effects on acid-base transport mechanisms are not well characterized in this segment. We found that recovery of cell pH (pH1) from an induced acid load (using NH4+) in single isolated segments of the initial portion ("bright") of the rabbit distal convoluted tubule (DCTb) was due to an ethylisopropylamiloride-sensitive Na+/H+ exchanger both in the absence and presence of HCO3-, but we found no evidence for participation of other mechanisms such as an H+ pump or an HCO3(-)-dependent mechanism. Introduction of calcitonin stimulated an Na(+)-independent, HCO3(-)-dependent mechanism (0.17 +/- 0.04 pH units/min, n = 14) that reestablishes normal pHi after an induced acid load. This mechanism was observed only in the presence of CO2/HCO3- and was not inhibited by N-ethylmaleimide (1 mM), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (200 microM), or Sch-28080 nor stimulated by glutamine (2 mM) or ketoglutarate (0.5 mM), but it was dependent on chloride. We conclude that, in the DCTb, salmon calcitonin activates a latent Na(+)-independent, HCO3(-)-dependent mechanism.