We studied the effects of 100 micrograms human pancreatic GH releasing hormone-44 (GRH) in 35 acromegalic patients. Plasma GH levels significantly increased [basal, 30 +/- 10 (SE) ng/ml; peak, 82 +/- 21 ng/ml; P less than 0.01], but a wide intersubject variability of the responses was found (range, 20-1602%). No relationship was found between the percentage GH increase after GRH and basal values of GH, PRL, or somatomedin-C. All patients also underwent an acute test with bromocriptine (2.5 mg orally) and TRH (200 micrograms iv). When dividing the patients according to their GH responsiveness to bromocriptine (Br), an inverse correlation (r = -0.42, P less than 0.05) was found between percentage of GH changes after GRH and after Br; moreover Br responder patients had a lesser (P less than 0.001) GH increase after GRH (124 +/- 27%) than nonresponders (562 +/- 116%). No relationship was found between the GH response to TRH and GRH, and no differences were found between the percentage GH increase after TRH (513 +/- 117%) and after GRH (349 +/- 71%). We conclude that the tumoral somatotrophs are sensitive to their specific releasing hormone and we suggest that the presence in the adenoma of cells with surface membrane receptors similar to those on the lactotropes may explain the lower sensitivity to GRH of Br responders compared to nonresponders.