Gluconeogenic activity in rat kidney cortex slices was stimulated by somatostatin. Somatostatin-stimulated gluconeogenesis was inhibited by phentolamine but not by propranolol suggesting that somatostatin action is mediated by ~-adrenergic stimuli. The stimulatory effect by this hypothalamic peptide was not seen when renal cortex slices were depleted of calcium. However, the effect could be recovered by the addition of calcium. The results suggest that stimulatory effect of somatostatin in renal gluconeogenesis is via e-adrenergic stimuli and that an increase in calcium influx into the cytosol may be the causative factor for the enhanced gluconeogenesis.