We have studied the effect of maximally inhibiting doses of dopamine (DA) or somatostatin on GH levels in 39 acromegalic patients. The GH-lowering effects of the two drugs were highly variable in different patients. A significant correlation (r = 0.45; P < 0.01) was found between the percent changes obtained during the infusions of DA (500 microgram/min) and somatostatin (3.33 microgram/min). Pretreatment with L-sulpiride markedly blunted the inhibitory effect of DA but did not affect the response to somatostatin. We conclude that the GH-secreting cells of acromegalic patients contain separate receptors for DA and somatostatin. We hypothesize that the partial or total lack of responsiveness to DA or somatostatin may be due to the loss of receptors for these agents on the GH-secreting neoplastic cells.