The role played by anions in salivary secretion has been studied in experiments on the isolated, perfused mandibular gland of the rabbit, in which perfusate Cl- and/or HCO3- were replaced by other anions. Replacement of Cl- with Br- had no significant effect on salivary secretion rate, but replacement with the other anions tested caused secretory rate to fall, by 38% (I-), 50% (NO3-), 61% (isethionate, ise -), and 66% ( CH3SO4 -), respectively. Replacement of perfusate Cl- with ise - or CH3SO4 - caused the salivary HCO3- concentration to rise up to 4-fold. Replacement with Br- or I- seemed to have little effect on salivary HCO3- concentration but, in contrast to ise -, Br- and I- entered the saliva in concentrations comparable to those of Cl- during control perfusion. In glands perfused with HCO3- and ise -, the addition of methazolamide, an inhibitor of carbonic anhydrase, caused a further 60% drop in secretory rate, but the saliva remained rich in HCO3-. Replacement of perfusate HCO3- with Cl- or ise - had no effect on salivary secretion or composition. Replacement of both HCO3- and Cl- in the perfusate with ise - reduced salivary secretion to less than 2% of control levels. In control glands (i.e. perfused with both HCO3- and Cl-), administration of furosemide, an inhibitor of Na+/Cl- co-transport, reduced the secretion rate and increased salivary HCO3- in a manner indistinguishable from that seen when perfusate Cl- was replaced with ise -. In control perfused glands, administration of SITS (4-acetamido-4'- isothio cyano-2,2'-disulphonic acid stilbene), an inhibitor of Cl-/HCO3- antiports , did not cause any change in salivary HCO3- concentration. Unexpectedly, it induced a significant increase in salivary secretory rate. The results show that salivary secretion depends on two independent transport systems. One is a Cl- -dependent, furosemide-sensitive system, probably a Na+/Cl- symport. The other is an HCO3- -dependent, methazolamide-sensitive system, and is probably an Na+/H+ antiport.