We studied the effect of a saline load on proximal tubular Na+, fluid and HCO-3 handling of control and uninephrectomized (UNx) rats. Glomerular filtration rate (GFR) was measured by inulin clearance, Na+ reabsorption in the proximal tubule by lithium clearance (CLi+), proximal tubule fluid reabsorption (Jv) by microperfusion with l4C inulin and proximal tubule HCO-3 reabsorption (JHCO-3) by estimating pH of perfusate and collected fluid in vitro under CO2 equilibrated oil by means of Sb microelectrodes. No significant differences were found between control and UNx animals in baseline values of urine flow, GFR, fractional water and sodium excretion and blood and urine pH and pCO2, showing that renal function was compensated 4 weeks after UNx. On the other hand, UNx rats showed a significant increase in proximal tubule Jv and JHCO-3. After extracellular fluid volume expansion (EFVE) by infusion of HCO-3 Ringer solution (0.1 ml/min) during 90-120 min, in both groups of animals hematocrit decreased by 15%, GFR remained unchanged and fractional Na+ and water excretion increased significantly. However, after EFVE Jv and JHCO-3 decreased significantly in control rats but were not modified in UNx animals. Fractional proximal Na+ reabsorption as measured by CLi+ decreased in control rats after EFVE and was not altered in UNx rats. After EFVE the fall in fractional distal Na+ reabsortion was significantly higher in control than in UNx rats. The present results provide evidence that after a saline load the impaired natriuretic response in UNx rats could be attributed to an alteration in proximal and distal tubular Na+ and HCO-3 handling. The data also showed a close correlation between proximal tubular function evaluated by CLi+ and by Jv.