1. The marked reduction in fractional lithium excretion (FELi) which accompanies chronic sodium depletion was investigated using free-flow micropuncture in anaesthetized rats which had been maintained in a sodium-depleted state for 8-10 days. 2. Compared with previous values in sodium-replete rats, sodium depletion was associated with small reductions in total and superficial nephron glomerular filtration rate and enhanced fractional reabsorption of water, sodium and lithium in the proximal convoluted tubule. 3. In untreated (sodium-depleted) rats, fractional deliveries of lithium (FDLi) to the late proximal convoluted tubule, early distal tubule and late distal tubule were 0.41 +/- 0.02, 0.20 +/- 0.01 and 0.18 +/- 0.02 (means +/- S.E.M.), respectively. Fractional lithium excretion (0.08 +/- 0.01) was significantly lower than late distal FDLi (P < 0.001). 4. Treatment with amiloride did not affect segmental lithium handling up to the late distal tubule. Frusemide had no effect on lithium reabsorption in the proximal convoluted tubule, but early distal FDLi (0.30 +/- 0.01) was raised compared with the untreated group (P < 0.001). Both diuretics eliminated the difference between late distal FDLi and FELi, respective values being 0.17 +/- 0.02 and 0.15 +/- 0.01 (amiloride-treated rats) and 0.31 +/- 0.02 and 0.34 +/- 0.02 (frusemide-treated rats). 5. These data indicate that part of the reduction in FELi in chronic sodium depletion is due to enhanced fractional fluid (and lithium) reabsorption in the proximal convoluted tubule. In addition, however, they provide direct evidence for amiloride-sensitive lithium reabsorption in the collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)