The principal problems related to the radioimmunoassay of calcitonin are discussed: the low circulating concentrations of the hormone in normal subjects; the heterogeneity of the circulating and tissular forms of the molecule; the diversity of the antibodies used and the restricted size of the antigenic site; the divergence between the biological and immunological domains. These findings have little incidence on the measurement of the hormonal concentration in subjects suffering either from medullary carcinoma of the thyroid or tumours producing the hormone ectopically. In contrast, determining the circulating levels of calcitonin in cases of eu- or hypocalcitonism are more problematic in view of the problems reported.