Cholinergically stimulated Cl and HCO3 transport in perfused rabbit mandibular glands has been studied with extracellular anion substitution and administration of transport inhibitors. In glands perfused with HCO3-free solutions, replacement of Cl with other anions supported secretion in the following sequence: Br = greater than Cl greater than I = greater than NO3 greater than isethionate. Furosemide, 1.0 and 0.1 mmol/l, inhibited Cl-supported secretion by 97-99% and 70-78%, respectively. SITS, 0.1 mmol/l, had no effect and amiloride, 1.0 mmol/l, caused a 55-65% inhibition. Addition of SITS to amiloride-treated glands produced no further effect. In glands perfused with Cl-free solutions, but containing 25 mM HCO3, amiloride, 1.0 mmol/l, inhibited secretion by 95% and methazolamide, 0.1 mmol/l, by 55%. In glands perfused with solutions containing both HCO3 and Cl, furosemide had smaller effects than in glands perfused with solutions containing only Cl - a dose of 1.0 mmol/l inhibited 60% of the initial fast phase of secretion, and 90% of the later plateau phase, while a dose of 0.1 mmol/l inhibited 30% of the initial phase, but had no effect on the plateau. SITS, 0.1 mmol/l, actually stimulated secretion by about 30%, but when infused in addition to furosemide (0.1 mmol/l), it inhibited by about 20%. Amiloride (1.0 mmol/l) caused no inhibition. The results suggest that there are at least three distinct carriers in the rabbit mandibular gland. One is a furosemide-sensitive Na-coupled Cl (probably Na-K-2Cl) symport, responsible for the bulk of normal secretion. The others are an amiloride-sensitive Na-H antiport and a SITS-sensitive Cl-HCO3 antiport.