We have investigated the effects of intravenous administration of a low dose of dopamine (DA) on plasma growth hormone (GH) concentrations in acromegalic patients and normal subjects with the aim of defining the somatotroph responsiveness to peripheral (i.e., outside the blood-brain barrier) specific dopaminergic stimuli. DA (0.02 µg/kg/ min) was infused for 180 min into 12 acromegalic patients and 10 normal subjects. DA infusion discriminated between two groups of acromegalics. In group I (n = 7), the elevated plasma GH levels (64.1 ± 29.9 ng/ml, mean basal value ± SEM) decreased significantly (mean overall GH inhibition, 26% reduction from basal levels; range, 10–49), whereas in group II (n = 5) plasma GH levels (29.8 ± 12.5 ng/ml) remained elevated (mean GH variation, 8% above baseline; range, 0–15). Plasma GH concentrations showed a significant rebound above baseline values after stopping DA infusion only in group I. In contrast, the responsiveness to TRH was not significantly different between the groups (percentage increase 767 ± 317% in group I vs. 382 ± 210% in group II) and they were also comparable with regard to sex, age, glucose tolerance, plasma prolactin (PRL) concentrations and adenoma size. However, the mean duration of the disease was significantly (p < 0.02) longer in group I (12.8 ± 2.6 years) than in group II (4.5 ± 1.5 years). Further, 3 patients with previous radiotherapy for invasive adenomas were nonresponders to DA. In normal subjects, DA infusion had no significant effect on plasma GH levels. It is concluded that: (1) somatotroph responsiveness to DA is not a constant feature of acromegaly. This responsiveness may be selectively altered in the cases of invasive and irradiated adenomas. (2) Peripheral specific DA stimuli does not increase GH release in