Severity of respiratory distress syndrome (RDS) and mechanical ventilation may affect the endogenous cortisol secretion in preterm infants. The aim of this study was to compare the serum cortisol concentrations of a relatively large and mature group of preterm infants with RDS who are ventilated or nonventilated and control preterm infants without RDS. Infants (group I) of comparable gestational ages without RDS served as controls. Infants with RDS who did not need ventilator support and surfactant therapy were considered to have mild RDS (group II). Those requiring mechanical ventilation and surfactant therapy were considered to have severe RDS (group III). Serum cortisol levels were determined after birth and on day 3 of life. The study groups consisted of 79 preterm infants with gestational ages ranging from 31 to 36 weeks, and birthweights ranging from 1086 to 1685 g. All preterm infants showed high cortisol levels after delivery regardless of respiratory distress (group I, n = 25, 34.1 +/- 10.7 mu g/dL; group II, n = 23, 33.6 +/- 12.0 mu g/dL; and group III, n = 31, 36.4 +/- 12.3 mu g/dL). In group III, the cortisol levels (50.8 +/- 16.8 mu g/dL) were higher than in group II (40.4 +/- 10.5 mu g/dL) and in controls (22.0 +/- 7.2 mu g/dL), and the cortisol levels of controls were lower than in group II on day 3 of life. Although the cortisol levels in severe and mild RDS infants increased significantly from their corresponding levels on day 1, they decreased in controls. The cortisol levels on day 3 of life were not significantly different in infants with poor outcome compared with infants with better outcome. Severity of RDS and mechanical ventilation were related to serum cortisol levels of preterm infants. Our study suggests that large and mature preterm infants who are ventilated and/or more severely ill release more cortisol than those less severely ill.