The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201–995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 μg. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 μg of SMS 201–995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P < 0.001 and P < 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P < 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P < 0.001) inhibited by previous sc injection of 50 μg of SMS 202–995. Pretreatment with 50 and 100 μ of SMS 202–995 sc (n = 9) inhibited (P < 0.001) the stimulatory effect of TRH (200 μg iv) on TSH without modifying basal levels. The injection of 100 μg/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials. Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation. With its high potency, slow plasma clearance, and long action SMS 201–995 may represent a valuable tool in the long-term management of states of inappropriate GH secretion.