The effects of long-term antiepileptic combined therapy with phenobarbitone (PB) and carbamazepine (CBZ) on the major endocrine functions were evaluated in a selected group of 15 young males with partial epilepsy. The plasma basal levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyrotropin (TSH), cortisol (CO), dehydroepiandrosterone-sulfate (DHEA-S), adrenocorticotropin (ACTH), growth hormone (GH), prolactin (PRL) and testosterone (T) were determined. TSH and PRL were also assessed in response to i.v. injection of thyrotropin releasing hormone (TRH). The results were compared with those found in 37 age-matched male volunteers. The most remarkable changes affected pituitary-thyroid axis and pituitary-adrenal axis, while the hypothalamic-pituitary response was normal. No correlation between hormonal changes and duration of epilepsy and therapy or ADs plasma levels was found. There seems to be considerable individual variability of response to antiepileptic therapy, probably depending on peripheral changes in the hormonal metabolism.