Objectives. To test the cortisol response to adrenocorticotrophic hormone (ACTH) in a population of very low birth weight newborns at the end of the first week of life, and to evaluate the relationship of this response to the subsequent development of bronchopulmonary dysplasia and to the total length of oxygen dependence. Methods. Appropriate for gestational age newborns <1500 g birth weight were enrolled prospectively. Response to ACTH stimulation was tested on days 5,6, or 7. Baseline cortisol, stimulated cortisol, and magnitude of response were compared between babies who developed bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 28 days, and those who recovered without BPD. Results. In this population, the cortisol response to ACTH increased with increasing birth weight (P < .001). Using birth weight as a cofactor, analysis of variance showed that patients who developed BPD (n = 34, BW 974 +/- 192 g, mean +/- S.D.) had significantly reduced responses to ACTH at 5 to 7 days of age compared to those who recovered (n = 25, BW 1251 +/- 194 g), P = .006. Additionally, 84% of patients who recovered without BPD, but only 26% of BPD patients, achieved a prospectively defined positive cortisol response to ACTH (greater than or equal to 9 mu g/dL; P < .005). Supplemental oxygen was discontinued at a younger postconceptional age in babies with a positive cortisol response to ACTH (P < .01) and fewer of those babies were on supplemental oxygen at 36-week postconceptional age (P < .01). Conclusions. At the end of the first week of life, infants who subsequently developed BPD and prolonged oxygen dependence had significantly lower cortisol secretion in response to ACTH than infants who recovered without BPD. We speculate that these babies may be unable to secrete adequate amounts of cortisol in a setting of increased stress, leaving them vulnerable to continuing lung injury.