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1. Changes in water and ion contents of rat renal cortical slices were followed over 4 hr incubation at 25 degrees C in potassium-free media and media with ouabain. Slices that lost potassium more rapidly swelled earlier. 2. Greater swelling with lower tissue potassium contents was also observed in slices preincubated and leached in potassium-depleting media and in slices incubated in lithium medium with 10 mM-ouabain and in potassium-free lithium medium with 10 mM-ouabain. 3. This swelling associated with potassium depletion was also observed when slices were incuabted in media where the substrate was malate in place of glucose. 4. No distinct fall in the oxygen consumption of potassium-depleted slices was detected during the period in which slices commenced swelling. 5. These results suggest that the swelling observed in potassium-depleted rat renal cortical slices is unlikely to be secondary to inhibition of cellular energy production.