Small for gestational age preterm infants have a higher risk of neonatal morbidity compared to appropriate for gestational age preterm infants. A diminished adrenal response to stress may be involved in the higher postnatal morbidity. The adrenal cortex response in relation to fetal growth was studied by ACTH stimulation tests in 43 preterm infants (born < or = 32 wk). The cortisol and 17-hydroxyprogesterone (17-OHP) responses to 1 microg/kg ACTH were analyzed in relation to birth weight SD scores (BW-SDS) corrected for gestational age, gender, and parity. BW-SDS was significantly associated with the cortisol and 17-OHP response. Infants with the lowest BW-SDS had the lowest cortisol levels after stimulation. No effect of size at birth was found on the ratio between cortisol and 17-OHP. In addition, basal cortisone levels in a single blood sample were higher in infants with the lowest BW-SDS than in infants with higher BW-SDS, but the ratio between cortisol and cortisone was comparable in the two groups. We conclude that the response of cortisol and 17-OHP to ACTH stimulation in preterm infants is related to fetal growth. The lack of influence of fetal growth on the ratio between cortisol and 17-OHP after ACTH stimulation suggests that the activities of 21- and 11 beta-hydroxylase are not affected. The lower adrenal response to stimulation may be important in neonatal morbidity and possibly the development of disease in later life in growth-restricted preterm infants.