We examined the effects of formate and oxalate on the rate of fluid absorption (Jv) in the rat proximal convoluted tubule in situ. Proximal tubules were microperfused with a high-Cl-, low-HCO3- Ringer solution (pH 6.7), and the peritubular capillaries were perfused with a standard Ringer solution (pH 7.4), simulating conditions in the late proximal tubule. Jv, a measure of transtubular NaCl absorption under these conditions, was calculated from the change in luminal [3H]inulin. Addition of formate in the physiological range (500 microM) to the luminal perfusate increased Jv by 45%; addition of 500 microM formate to both luminal and capillary perfusates increased Jv by 57%. Similarly, addition of oxalate in the physiological range (5 microM) to the luminal perfusate increased Jv by 37%; addition of 5 microM oxalate to both luminal and capillary perfusates increased Jv by 57%. The stimulatory effects of formate and oxalate perfused in the lumen and capillaries were not additive. Addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS, 0.1 mM) to the luminal perfusate had no effect on baseline Jv measured in the absence of added formate and oxalate but completely abolished the increment in Jv induced by formate and oxalate. Addition of the Cl(-)-channel blocker diphenylamine-2-carboxylate (DPC, 0.2 mM) to the capillary perfusate had no effect on baseline Jv but completely abolished the increment in Jv induced by formate and oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)