The effect of somatostatin on the catecholamine (CA) release from the chromaffin cells was determined on the isolated dog adrenals perfused with 1.8 mM Ca2+ containing fluid except indicated. The extremely low concentrations of somatostatin (0.18 nM-18 nM) were found to stimulate acetylcholine (Ach, 5 microM)-evoked CA release with the maximum response (by 114% above control) at 1.8 nM but the relatively high concentrations (61, 610 nM) caused an inhibition. Somatostatin (6.1 nM) also facilitated excess K+ (15 mM)-induced CA release but failed to enhance the release evoked by a Ca2+ ionophore, A23187 (50 microM) and the release by caffeine (50 mM) under the condition of Ca2+-free. Somatostatin by itself did not affect significantly on the basal release of CA. Elevation of Ca2+ concentrations from 1.8 mM to 5 mM in the perfusion fluid reduced the stimulatory and inhibitory effect of somatostatin. It is possible that somatostatin enhances CA release by facilitating the influx of Ca2+ via the potential-sensitive permeability channel when chromaffin cells are depolarized. The present results provide the first demonstration that somatostatin stimulate the release of CA from the adrenal gland suggesting that somatostatin may function as a facilitatory modulator of the response to ACh at chromaffin cells.