1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate (GFR) of the kidney that remained in the donor rose from 45 +/- 10 (mean +/- SD) to 59 +/- 10 ml/min (P less than 0.01) 5 days after contralateral nephrectomy and remained at this level through the observation period. 3. The lithium clearance (CLi) of the remaining kidney rose from 11.6 +/- 3.7 to 20.5 +/- 8.2 ml/min (P less than 0.01) and remained significantly elevated throughout the observation period. 4. Absolute proximal fluid reabsorption rate (APR), which was estimated as GFR minus CLi, was unchanged 5 days after contralateral nephrectomy, but then rose gradually to reach significantly elevated levels after 4 weeks. 5. Fractional proximal reabsorption (FPR; APR/GFR) fell from 0.75 +/- 0.06 to 0.66 +/- 0.11 (P less than 0.01) but subsequently rose to levels not significantly decreased from normal. 6. Twenty-four hour fractional clearances of beta 2-microglobulin, albumin and immunoglobulin G rose markedly on the day of nephrectomy, peaked at 2-3 days and subsequently fell to moderately elevated levels. 7. Both the CLi and the plasma protein clearance studies demonstrate that the early response of the remaining kidney to contralateral nephrectomy in man is an increase in GFR, an unchanged APR and a fall in FPR. The proximal tubules thus initially handle the increased filtrate load by passing it on to more distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)