Desacetyl alpha-melanocyte-stimulating hormone (MSH) (ACTH 1-13) is the main form of immunoreactive alpha-MSH circulating in human plasma. This study evaluates the possibility that a dopaminergic inhibitory mechanism could be operative during human development. Thus, alpha-MSH and ACTH 1-13 plasma levels were measured after dopaminergic blockade (domperidone (0.3 mg/kg body weight, maximum 10 mg, p.o.) in 13 prepubertal (aged 4.5-12.3 y) and 12 pubertal (aged 10.2-16.9 y) children. Both peptides were measured by RIA after plasma extraction on Sep-pak C-18 cartridges and reverse phase HPLC. The chromatographic profile of alpha-MSH immunoreactivity falls into two main peaks, corresponding to the retention time of alpha-MSH and ACTH 1-13. Moreover, in prepubertal children domperidone induced a significant increase of alpha-MSH from 1.7 (median) to 5.0 pmol/L, whereas no changes in alpha-MSH plasma levels were found in pubertal subjects (from 5.0 to 4.1 pmol/L). Similarly, ACTH 1-13 plasma levels significantly increased from 3.0 to 19.8 pmol/L in prepubertal children remaining stable in pubertal ones (from 7.8 to 4.6 pmol/L). Moreover, a significant negative correlation was found between basal DHEA-S levels and the plasma alpha-MSH increase after domperidone. These data demonstrate that: 1) ACTH 1-13 is the main form of immunoreactive alpha-MSH in prepubertal life and 2) the dopaminergic inhibition of both ACTH 1-13 and alpha-MSH plasma levels is apparent only in prepubertal subjects.