Hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in anorexia nervosa (AN) has been demonstrated and is likely to reflect a central nervous system (CNS)-mediated effect of starvation. Alterations in the adrenal response to ACTH in AN have also been reported by some authors. In order to define the adrenal sensitivity to ACTH in this condition, we studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of low and supramaximal ACTH 1-24 doses (0.06 microg/m2 ACTH 1-24 iv at 0 min and 250 microg ACTH 1-24 iv at +60 min, respectively) in 10 young women with AN [ANW, age 21.2 +/- 0.9 yr, body mass index (BMI) 15.7 +/- 0.6 kg/m2]. The results in this group were compared with those recorded in 10 healthy normal women (HW, 23.4 +/- 1.1 yr, 21.9 +/- 0.9 kg/m2). In ANW urinary F levels were similar to those in HW. Basal serum F, A and DHEA levels in ANW were not significantly different from those in HW. In HW the lowest ACTH dose induced a significant (p<0.05) increase of F, A and DHEA. The maximal ACTH dose induced F, A and DHEA increases greater (p<0.05) than those induced by the lowest ACTH dose. In ANW both ACTH doses induced significant (p<0.05) F and DHEA increases which were not significantly different from those in HW, though a trend toward a lower cortisol response after ACTH 0.06 microg/m2 in ANW was present. Like in HW, in ANW the maximal ACTH dose induced F and DHEA increases greater (p<0.01) than those induced by the lowest dose. Unlike HW, in ANW A levels did not increase after the lowest ACTH dose while they increased after the maximal one overlapping the response in HW. In conclusion, the cortisol and DHEA responses to a very low and a supra-maximal ACTH dose in patients with AN were similar to those in healthy subjects, indicating that the sensitivity to ACTH of the fasciculata and reticularis adrenal zones is preserved in this condition. On the other hand, a reduced sensitivity to ACTH of the glomerularis adrenal zone in patients with AN is suggested by the lack of aldosterone response to the lowest corticotropin dose.