There are few published data on plasma ACTH and cortisol in very low birth weight (VLBW) infants beyond the first week of life. We therefore measured plasma ACTH and cortisol longitudinally in 25 infants (mean birth weight 1025 g, mean gestational age 28 weeks) at 1, 2, 4 and 8 postnatal weeks to document normative values for infants not receiving dexamethasone. We also examined the influence of clinical state and dexamethasone treatment on plasma ACTH and cortisol levels. Median plasma ACTH increased significantly with advancing postnatal age from 1 week to 8 weeks (21.0 vs. 40.0 ng/l; P = 0.01) but did not correlate with postconceptional age. Median plasma cortisol decreased significantly with advancing postnatal age from 1 week to 8 weeks (216 vs. 50 nmol/l; P = 0.001) and correlated inversely with postconceptional age (P = 0.004). At 8 weeks infants who were clinically well (n = 6) had lower plasma ACTH values compared with sick (n = 6) infants (median: 37.0 vs. 63.5 ng/l; P = 0.033). Plasma ACTH did not correlate with clinical state at 1, 2 and 4 weeks. At none of the postnatal ages studied was plasma cortisol influenced by the degree of sickness. Five infants received dexamethasone to assist weaning from mechanical ventilation. Their median plasma ACTH level, at 8 weeks, was significantly lower than that of the 12 infants who did not receive dexamethasone (11.0 vs. 40.0 ng/l; P = 0.0006). Plasma cortisol was not significantly influenced by dexamethasone treatment (P = 0.27). These data provide further information on the evolution of adrenocortical function in VLBW infants in the first months of life.