Human pancreatic growth hormone releasing factor 1-44 (hpGRF), 100 micrograms was administered as an i.v. bolus injection to eleven patients with acromegaly. The mean serum growth hormone (GH) levels rose (P less than 0.001) from 54 +/- 20 ng/ml to 215 +/- 126 ng/ml (+/- SEM) 20 min after the injection. Although the maximum response of GH levels was highly variable it correlated positively with the individual GH levels (P less than 0.01, Rs = +0.80). Thus the higher the GH levels, the greater the responsiveness to hpGRF. Administration of somatostatin (SRIF), 300 micrograms/h, lowered basal GH levels from 76 +/- 38 ng/ml to 13 +/- 5 ng/ml (P less than 0.01) after 1 h. hpGRF administration during concomitant SRIF infusion also led to highly variable growth hormone responses. The maximum GH responses again correlated positively with the GH level before hpGRF after 1 h of SRIF administration (P less than 0.05, Rs = +0.79). GH responses to hpGRF were completely blocked by SRIF in three out of four patients whose GH levels decreased to normal levels during SRIF infusion. Our data illustrate that the pituitary in acromegaly is normally responsive to both SRIF and hpGRF but at a higher setting of basal GH levels.