Glucagon-induced growth hormone (GH) secretion was studied in healthy subjects under basal conditions (n = 18), and when treated with TRH (n = 10), cyproheptadine (n = 8) and pimozide (n = 6). With glucagon alone, the mean serum GH level significantly increased at 150 minutes and at 180 minutes. TRH administered as a bolus injection completely suppressed the GH response to glucagon. Cyproheptadine pretreatment resulted in a substantial suppression of the GH response to glucagon. A significant difference between basal and post-cyproheptadine GH levels was observed at 150 minutes after glucagon. Pimozide pretreatment was followed by a reduction of GH response to glucagon, but the difference between control and pimozide-treated groups was not significant. In conclusion, it is proposed that glucagon-induced GH secretion is at least partly mediated via serotoninergic mechanisms while significant dopaminergic involvement does not seem probable. It is further suggested that TRH plays a substantial inhibitory role in glucagon-stimulated SH secretion.