The present experiments were undertaken to investigate the effect of alterations in extracellular Ca++ concentration on glucagon release from the isolated perfusedrat pancreas.In control studies using perfusate containing 5.0 mEq/1 Ca++,arginine (19.2 HIM) alone or withglucose (100 mg/100 ml) caused biphasic glucagon release. Insulin responses to arginine alone were monophasic whereas arginine plus glucose caused biphasic insulin release. During perfusion with Ca++-free medium, glucagon releasewas inhibited > 90% and insulin release was inhibited about 75%. Subsequent introduction of 5.0 mEq/1 Ca++ to medium during stimulation of previously Ca++-depleted pancreases promptly restored glucagon and insulin responses toward control levels. Thus, like other endocrine tissue, the pancreatic alpha-cell requires calcium for normal secretory function. (Endocrinology94: 1381, 1974)