The composition of the renal papilla, medulla and cortex was studied in rats during hydropenia and water diuresis, and a few observations were made on hamsters.In confirmation of earlier findings, osmolality increased progressively from the outer medulla towards the tip of the papilla in hydropenia; this osmolal gradient was due largely to increasing concentration and content of sodium and urea. The osmolality at the tip was close to that of simultaneously collected urine. In water diuresis, this osmolal gradient was smaller but still present.Ammonium content and concentration increased progressively from the outer medulla towards the papilla.In water diuresis, the concentration and content of urea fell, but the gradient was still present. Sodium was little altered, and the fall in ammonium content, though considerable, contributed little to the total osmolal change.Potassium concentration and content were high in the terminal segment in diuresis and antidiuresis, and in water diuresis exceeded the hydropenic value.The water content increased progressively from the outer towards the inner medulla, but at the tip it was lower than in the adjacent segment. This distribution was qualitatively similar in both conditions, but the absolute level was higher in all medullary segments in water diuresis.The results are discussed in relation to the mechanism of production and maintenance of medullary hypertonicity. O'Dell, 1959, sheep, 1961, beaver, rabbits and psammomys; Eigler et al., 1962, rats; Levitin et al., 1962, dogs] have revealed that the sodium and urea concentration rises progressively from the cortico-medullary junction towards the medulla and papilla. It is clear from chemical, cryoscopic [Wirz et al., 1951; a] and direct micropuncture [Wirz, 1953[Wirz, , 1957Gottschalk and Mylle, 1959;Gottschalk, 1961;Lassiter et al., 1961] studies that in hydropenia the osmolality of medullary interstitial fluid rises progressively from the cortico-medullary junction towards the medulla and papilla.Observations during water diuresis are fewer. The medulla is still hypertonic to plasma in dogs [Ullrich et al., 1955;Ullrich and Jarausch, 1956;Levitin et al., 1962], and in rats , but the mechanism involved in establishing the differences between hydropenia and water diuresis is poorly understood.In an attempt to elucidate the mechanism involved, the chemical composition of cortex, medulla and papilla of rats and hamsters was analyzed during hydropenia and water diuresis. In particular, the relative contributions of sodium and urea, and the variation in water content, were studied.