A spontaneous diuresis that precedes the improvement of pulmonary function has been described in patients with respiratory distress syndrome (RDS). The developmental changes in renal physiology responsible for this spontaneous diuresis are not completely understood. To describe the mechanisms responsible for the spontaneous diuresis, serial renal function studies were performed during the first five days of life in nine premature neonates with RDS. Diuresis was defined as a urine output that was at least 80% of fluid intake; prediuretic, diuretic, and postdiuretic periods were observed in all study infants. Oxygenation did not improve until the postdiuretic period. Renal function studies disclosed a significant increase in free water clearance during the diuresis with the production of dilute urine and a reciprocal rise in serum sodium concentration and plasma osmolality. The glomerular filtration rate increased at the onset of diuresis and remained elevated after the diuresis ended; however, the proportion of filtrate excreted was significantly elevated during the diuresis compared with prediuretic and postdiuretic values. These data suggest that the diuresis in patients with RDS is a water diuresis secondary to an endogenous water load.