Lithium clearance is often used as a marker for proximal tubular water transport. Proximal tubular transport may be modulated by changing plasma potassium concentration. The aim of the present study was to examine the effect of acute changes in plasma potassium concentration on proximal tubular fluid and lithium transport. Clearance studies were performed in seven anaesthetised, volume-expanded dogs treated with amiloride (1 mg kg-1 body weight) to block distal tubular potassium secretion, and with bumetanide (30 micrograms kg-1 body weight) to inhibit sodium reabsorption in Henle's loop. When plasma potassium concentration was raised from 2.6 +/- 0.2 to 7.9 +/- 0.2 mmol l-1, water reabsorption decreased from 23.9 +/- 2.9 to 19.8 +/- 2.2 ml min-1, whereas lithium reabsorption increased from 10.5 +/- 2.3 to 18.1 +/- 2.3 mumol min-1, at constant glomerular filtration rate. We conclude that acute elevation of plasma potassium concentration inhibits proximal tubular fluid reabsorption, but stimulates renal lithium reabsorption. Thus, lithium reabsorption cannot be used as a marker for proximal tubular transport during acute changes in plasma potassium concentration.