The anomalous GH response to TRH or glucose loading was evaluated in patients with severe liver disease untreated or pretreated with metergoline (MCE), a potent antiserotoninergic drug. In 9 patients, injection of 400 micrograms TRH as a bolus induced a clear-cut GH rise (> 8 ng/ml), with peak levels 15-90 min post injection. Pretreatment with MCE did not modify baseline GH levels but potentiated the TRH-induced GH rise in 4 patients. In addition, 2 of 8 TRH nonresponder patients developed the anomalous GH response after MCE pretreatment. Like MCE, methysergide, another antiserotoninergic drug, potentiated the TRH-induced GH rise in 2 of 4 patients. Glucose administration (100 g, orally) induced a paradoxical rise of GH in 9 of 10 patients; after MCE, the paradoxical GH response to glucose was potentiated in 6 patients. These data provide the first experimental evidence that a derangement in brain monoamine (serotonin) function is actually involved in the occurrence of anomalous GH responses in subjects with severe liver disease.