The effects of a new somatostatin analogue SMS 201-995 (H-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol), Sandostatin) on the orthostatic stimulation of plasma renin activity (PRA) following head-up tilting and on angiotensin II (Ang-II) induced aldosterone (PA) release were studied under placebo controlled conditions in separate groups of healthy volunteers consisting of six and 10 subjects, respectively. Head-up tilting (by 60 degrees) produced the characteristic increases in PRA and PA. Administration of SMS 201-995 significantly (P less than 0.05) inhibited this PRA elevation from 30 min on. Throughout the study period, PA levels were not consistently altered by this analogue. Furthermore, SMS 201-995 failed to inhibit the stimulation of PA secretion induced by exogenous angiotensin-II (2-10 ng/kg/min). Results presented here are at variance with data collected with natural somatostatin showing an inhibitory effect on stimulated PA. This discrepancy can be explained by the recently described absence of SMS 201-995 binding sites in primate adrenal cortex and in human aldosteronomas.