The work relates to our understanding of the biochemical events associated with the normal function of the thyroid and to pathological conditions of the thyroid, such as in Graves' disease. The work began with a study of the effect of thyrotropin (TSH) on iodide transport mechanisms. The work has evolved in several directions: (1) A detailed study of protein synthesis reflecting mRNAs induced by TSH and cyclic AMP. (2) Isolation from FRTL-5 thyroid cells of a low molecular weight iodoprotein associated with autoregulation of iodide transport. (3) Study of effects on iodide fluxes related to receptor activation by a variety of ligands. The work has linked inositol phosphate production with iodide efflux and calcium mobilization induced by TSH and norepinephrine through alpha-receptor activation. The mechanism of TSH- and norepinephrine-stimulated iodide efflux has been related to the metabolism of arachidonic acid via the lipooxygenase or epoxygenase pathway and related to thyroglobulin iodination and thyroxine formation. (4) The mechanism of iodide fluxes in throid cells has been further characterized using stilbene derivatives that specifically block anion channels, and using monoclonal antibodies directed against the chloride channel of red blood cells. The work continues to support the hypothesis that alterations in ion fluxes are important early events, as well as primary actions of TSH and pharmacological agents.