The acute effect of the somatostatin analog SMS 201-995 (SMS) was investigated in eight acromegalic patients. This substance is an octapeptide [DPhe-Cys-Phe-D-Trp-Lys- Thr-Cys-Thr-(ol)] that inhibits GH release in experimental animals and man. After a control day, 50 μg SMS were injected sc, and plasma GH and insulinand blood glucose levels were measured at multiple intervals for 24 h. GH significantly (P < 0.001) decreased in seven of eight acromegalic patients from 30 ± 5 (±SE) toan average of 10.7 ±4 μg/1 from –10 h after drug administration. No rebound effect occurred. Postprandial blood glucose levels were significantly (P < 0.01) higher between 2 and 4 h after SMS treatment compared with control day values, and there was a substantial reduction in insulin secretion, as estimated by the area under the curve(P < 0.01), during the first 3 h after SMS administration. Circulating GH was notaltered by SMS or the dopamine agonist mesulergine in one patient, butthe combination of both substances (50 μg SMS, sc, and 0.5 mg mesulergine, orally) reduced GH to below 50% of basal. In vitro studies showed that 1 pM, 0.1 nM, and 10 nMSMS or natural somatostatin exerted a similar inhibitory effect (12–39%reduction; P < 0.01 for all three strengths) on GH release by cultured human pituitary tumor cells. In conclusion,the somatostatin derivative SMS exerts a potent and prolonged inhibitory action on GH secretion and a shorter lasting suppression of insulin in acromegalic patients. Therefore,it may represent a useful tool in the chronic management of this condition.(J Clin Endocrinol Metab60:1161,1985)