The effect of calcitonin (CT) on serum glucose and insulin secretion was investigated in rats. CT administration [s.c.] (80 MRC [Metabolic Research Council] mU/100 g body wt) produced a significant increase in serum glucose, while it did not significantly alter serum insulin in fed rats. A marked elevation of insulin secretion after a single i.p. administration of glucose (0.1 g/100 g) in fasted rats was not significantly altered by the treatment with CT. When both CT and somatostatin (250 .mu.g/100 g) were administered s.c. simultaneously, the serum glucose level increased significantly compared with that of rats given somatostatin alone. The progressive increase in serum glucose caused by CT was significantly inhibited by s.c. insulin administration (0.1 U/100 g). Apparently CT increases serum glucose concentration independently of insulin secretion in rats.