Acromegalic subjects (30) underwent chronic CB154 therapy (10-20 mg daily) for periods ranging from 3 mo.-2 yr. In 18 out of 21 patients, who exhibited consistent HGH [human growth hormone] reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50% of base line values, e.g., from mean daily values between 14-197 ng/ml (mean .+-. SEM [standard error of the mean] = 57.8 .+-. 12.4 ng/ml pre-treatment) to 2-19 ng/ml (mean 8.3 .+-. 1.2 ng/ml post-treatment). In 12 of the subjects who responded to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidence with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH [thyrotropin releasing hormone] or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g., reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma P after insulin, decreased urinary excretion of phosphate, hyperhydroxyprolinuria and hypercalciuria. Collectively, these data demonstrate that CB154 therapy is effective in reducing HGH hypersecretion in many acromegalic patients during long-term treatment.