It is known that rats treated, at neonatal age, with monosodium L-glutamate (MSG) develop neuroendocrine and metabolic abnormalities, resulting in a phenotype of hypothalamic obesity, characterized by increased adiposity, corticosteronemia and leptinemia. OBJECTIVE: We explored whether adrenal manipulations could result in the reversion of this phenotype of hypothalamic obesity. EXPERIMENTAL DESIGNS: Newborn male rats, treated with MSG or vehicle (CTR), were submitted to sham operation, bilateral adrenalectomy (ADX) or bilateral adrenal enucleation (AE) on day 120 of age. Animals were examined 21 days after ADX, combined or not with corticosterone (B) substitution (ADX+B), and on days 21 and 35 after AE. Food intake, body weight and body fat mass were monitored; additionally circulating levels of insulin, leptin, ACTH and B were measured. RESULTS: Our data indicate that: a) normalization of basal B circulating levels in, 21 day-ADX and -AE, MSG rats fully reversed hyperinsulinemia, hyperleptinemia and significantly decreased body fat mass; and b) recovery of hypercorticosteronemia in, 35 day-AE, MSG rats fully restored this phenotype of hypothalamic obesity. CONCLUSION: Our study strongly supports that high glucocorticoid production is the main factor responsible for the development of enhanced adiposity in MSG rats and, importantly, that this abnormality could be reversed by an appropriate therapy.