To evaluate the relationship between improvement in pulmonary function and spontaneous diuresis in respiratory distress syndrome, nine premature infants requiring mechanical ventilation for RDS were studied at a mean age of 11.9 hours prior to the onset of diuresis, at onset of diuresis, at maximum urine output (mean age 44.9 hours), and at 24 hours after maximum urine output. Prior to diuresis functional residual capacity decreased from mean +/- SEM of 16.2 +/- 2 to 13.3 +/- 1.2 ml/kg, and dynamic lung compliance decreased from 2.5 +/- 0.3 to 1.8 +/- 0.3 ml/cm H2O (P less than 0.05), indicating that the respiratory disease was worsening. There was no significant change in alveolar-arterial oxygen gradient, peak inflating pressure, or rate of intermittent mandatory ventilation over this period. At the time of maximum urine output, however, FRC had increased 36% (P less than 0.05). CL had increased by 60% to 2.8 +/- 0.4 ml/cm H2O (P less than 0.025), AaDO2 had decreased from 246 +/- 27 to 184 +/- 30 torr (P less than 0.005), and PIP had decreased from 14.9 +/- 2.2 to 11.3 +/- 2.1 cm/H2O (P less than 0.05). On follow-up study 24 hours after maximum urine output, there was no further significant improvement in FRC, CL or PIP, but IMV rate and AaDO2 continued to decrease. These data show that the pulmonary function in RDS deteriorates until the onset of diuresis, after which it rapidly improves. This diuresis may represent the removal of excess lung liquid and seems necessary for improvement in RDS.