It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500 micrograms, iv), gonadotropin-releasing hormone (LHRH) (100 micrograms, iv) and GH-releasing hormone (GHRH) (100 micrograms, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100 micrograms, iv) with or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to +30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7) M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12, 83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)