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1. The time course and extent of changes in the composition of renal tissue slices in osmotic diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of mannitol (15 g/100 ml.) for up to 7 hr.

2. Very rapid changes in tissue water and solute contents occurred within 15 min, preceding the times of maximal diuresis, with little subsequent change even up to 7 hr.

3. The main changes were:

(a) an increase in water content in all slices, particularly the papilla; (b) a very profound decrease in papillary and medullary urea content in the first 15 min, with a small, but significant, further decrease, subsequently; (c) a small, but significant, rapid decrease in papillary sodium, and small non-significant increases in the outer medulla and cortex. Subsequent changes in any segment were small and non-significant; (d) apart from small changes in the first 15 min ammonium and potassium contents remained fairly constant.

4. The rates of change in papillary and urinary urea concentrations were similar, so that after 30 min, any differences between tip and urinary concentrations were small and non-significant.

5. The findings are discussed in terms of factors influencing counter-current mechanisms. It is concluded that altered medullary blood flow is mainly responsible for the rapid changes in medullary composition.

6. The relation between papillary and urinary urea concentrations is explicable in terms of passive handling, with equilibration across a freely permeable collecting duct membrane.