Plasma GH responses to GH-releasing peptide (GHRP) were studied in 11 patients with active acromegaly. Ten of these patients showed plasma GH increases to GHRP (100 μgs i.v.), whereas every patient showed GH increases to TRH (500 μgs i.v.) and GHRH (100 μgs i.v.). When GHRP was administered together with GHRH to the 10 GHRP responders, plasma GH responses were synergistically enhanced. However, combined administration of GHRP and TRH did not enhance the response. The GH response pattern and mean time to the peak value were similar to TRH but were different from GHRH. There was no correlation in the maximum GH increment between GHRP and TRH or GHRP and GHRH. It is concluded that GHRP stimulated GH release in the majority of acromegaly patients. The mode of action of GHRP might be similar to TRH and different from GHRH, although the sites of action of GHRP seemed to be different from those of TRH and GHRH.