Evidence exists that the serotoninergic system influences the hypothalamo-pituitary-adrenal axis and pituitary GH secretion. The effect was investigated of chronic (9 weeks) administration of the serotonin receptor agonist dexfenfluramine (DF) (15 mg twice daily) versus placebo on both systems in 24 moderately obese patients with an overconsumption of snacks. Before as well as after treatment, 100 μg GHRH and 100 μg CRH was administered iv. Weight loss after 9 weeks was 3.1±2.3 kg in the DF group and 0.1±1.2 in the placebo group (p<0.001). No significant difference between the changes in the apparently normal ACTH and Cortisol response in both groups was found. The apparently low GH response did not increase or normalize, but on the contrary decreased further after DF. No changes were shown in urinary free cortisol excretion and serum IGF-I levels. It can be concluded that in moderately obese patients the use of DF during a 9-week period induced a significant weight loss, did not influence the responsiveness of the pituitary gland to CRH nor the overall activity of the pituitary adrenal axis and finally, did not normalize the blunted GH response after GHRH. © 1995, Italian Society of Endocrinology (SIE). All rights reserved.