1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function.
2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of lithium or influence of osmotic diuresis.
3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min.
4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min.
5. Lithium clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment.
6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct). With more severe impairment the proximal tubule also becomes involved in the adjustment.