Somatostatin is a potent inhibitor of the growth hormone (GH) secretion. However, the short half-life as well as the rebound phenomenon have rendered it impractical for therapeutic use. SMS 201-995, a long acting somatostatin analogue, has been shown to have a long acting inhibitor effect on GH secretion. To observe its suppressive effect on GH secretion and to determine whether it has a diabetogenic effect and whether it can suppress the paradoxical response of GH, we administered 50 μg of SMS 201-995 subcutaneously to five acromegalic patients before breakfast. Serum GH was reduced 85% from the basal concentration four hours after the administration of SMS 201-995 and remained below the basal level for up to eight hours without a rebound phenomenon. The pattern of glucose intolerance was observed in 4 out of 5 patients but not in the normal controls; it seemed to be caused by exessive GH. Also SMS 201-995 did not suppress postprandial insulin and glucagon secretion. In addition, we observed that SMS 201-995 suppressed the paradoxical release of GH to TRH in two of three patients who showed a paradoxical response. Unexpectedly one patient who had no paradoxical response before the administration of SMS 201-995 showed a paradoxical response. In conclusion, we suggest that more than 50 μg of SMS 201-995 should be given at least 3 times a day for adequate adjunctive therapy of acromegaly. The SMS 201-995 has no diabetogenic effect.