The syndrome of familial medullary thyroid carcinoma is inherited as an autosomal dominant trait and is characterized by the development of bilateral and multicentric C-cell and adrenal medullary tumors. Sequential clinical screening studies for determination of calcitonin and catecholamine levels in these kindreds, combined with correlative pathological analyses, have led to the concept that both these tumors are preceded by relatively long pre-neoplastic phases of C-cell and adrenal medullary hyperplasia. The human tumor system, together with similar experimental animal models, provides an opportunity to study the early phases of neoplastic growth and to delineate the differences between physiological and pre-neoplastic (pathological) hyperplasia in vivo and in vitro. Alterations in cell junctions (desmosomes), abnormalities in the basal lamina, and heterogeneity in secretory granule morphology will be correlated with tissue and serum calcitonin heterogeneity and other peptide hormone production by radioimmunoassay, immunocytochemistry and morphometric analyses, with the progressive phases of pre-neoplastic and neoplastic development. In vitro studies of the effects of various agents on modulation of peptide hormone synthesis and secretion will be undertaken in normal, hyperplastic and neoplastic cells.