The clearance of lithium was analyzed in relation to the glomerular filtration rates and the effective renal plasma flow in 41 patients with renal disease and variable degree of renal functional impairment and in 40 normal subjects. In the patients, there was on average a 35% decrease of glomerular filtration rates (109 +/- 64 [SD] ml/min) and renal plasma flow (490 +/- 275 ml/min) and a 25% decrease of lithium clearance (22 +/- 12 ml/min); the lithium clearance correlated closely with the glomerular filtration rates and renal plasma flow (r = 0.69; p less than 0.001). The absolute proximal reabsorption of fluid was decreased by 38% (89 +/- 56 ml/min) while the distal absolute reabsorption of sodium (21 +/- 12 ml/min) was unchanged. Individual values of fractional proximal or distal reabsorption as related to glomerular filtration rates or renal plasma flow were equally distributed between normal and renal subjects, except in the presence of a severe renal function impairment, where both variables decreased exponentially. This suggests that in renal failure, sodium balance is maintained by a proportional decrease of proximal and distal sodium reabsorption in relation to glomerular filtration. Only in the presence of severe renal failure (GFR less than 30 ml/min) both variables are concomitantly readjusted to lower values.