The relative distribution of somatostatin- and calcitonin-containing cells in thyroid glands from various mammalian species was investigated by immunoperoxidase staining, and the concentration of immunoreactive somatostatin by radioimmunoassay. In the thyroid glands of guinea pigs and rabbits, most of the calcitonin cells were also immunoreactive to the somatostatin antiserum, and high concentration of immunoreactive somatostatin was obtained. On the other hand, in the thyroids of other animal species—rats, dogs, pigs, cows, goats, cats, monkeys, mice, and hamsters—only a few C cells revealed the immunoreaction for somatostatin, and the concentration of somatostatin was low. In all animal species studied, the somatostatin was present in the same cells that contain calcitonin, though in guinea pigs and rats there were some C cells containing a large number of reaction products for somatostatin but very few for calcitonin. Thus, it was concluded that there was a considerable variation in somatostatin immunoreactivity of thyroid C cells from species to species.