To explore further the mechanism of the effect of dietary NaCl intake on collecting duct (CDS) chloride uptake, we compared late distal chloride delivery to and urinary 36Cl recovery (the latter as an index of unidirectional efflux) from the CDS in four groups of male Sprague-Dawley rats. Groups were prepared for 7-10 days as follows: group 1, drinking 0.15 M NaCl; group 2A, regular diet; group 2B, regular diet plus deoxycorticosterone (2 mg im) (at 24 and 2 h before micropuncture); and group 3, low-NaCl diet. To increase tubule fluid flow rate and produce natriuresis without chloruresis, 0.15 M NaHCO3 at 5% body wt/h was infused in all groups except group 3, in which an infusion of 150 mM Na+, 55 mM Cl-, and 85 mM HCO3- was required to maintain a plasma chloride concentration equal to that in other groups. Plasma chloride concentration and arterial pH did not differ between groups before infusion. Urinary 36Cl recovery increased in parallel with dietary NaCl content (P = 0.0001). By analysis of multiple covariances, neither tubule fluid chloride concentration nor chloride delivery to the CDS correlated with urinary 36Cl recovery within any of the groups or for all animals studied. High doses of mineralocorticoid did not alter chloride uptake in group 2. These data suggest that progressive restriction of dietary NaCl enhances chloride uptake in the CDS of the rat unrelated to changes in plasma chloride concentration or chloride delivery from the superficial late distal tubules.