Summary. 4-hydroxybenzoic acid methyl ester (methylparaben) inhibits organification of iodide by isolated hog thyroid cells. The concentration which produces a 50% inhibition was about 2.0 x 10-4M. A similar inhibition was observed in nonstimulated and TSH-or dibutyryl cyclic AMP-stimulated cells. Neither iodide uptake nor cyclic AMP generation were altered by methylparaben.Antithyroid drugs refer to a group of compounds that block the synthesis of thyroid hormones. These compounds fall into 2 main categories: a) compounds that inhibit accumulation of iodide by the thyroid gland, b) compounds that interfere with the utilization of iodide into the gland. The compounds of the 2nd group exert their inhibitory effect by blocking one or several of the following reactions: oxydation of iodide, formation of iodotyrosines, coupling of iodotyrosines to form thyroid hormones. Besides, thionamides which are the most potent antithyroid agents, phenol and benzoic acid derivatives (resorcinol, p-aminobenzoic acid ...) are known to be efficient inhibitors of iodine metabolism both in vivo and in vitro. During the course of our study on the metabolism of iodide in dispersed thyroid cells, we found that 4-hydroxybenzoic acid methyl ester, a compound used as a food or drug preservative, prevented thyroid hormone synthesis. In this communication we report that this compound inhibits the organification of iodide without altering the iodide trapping mechanism. Suspensions of dispersed hog thyroid cells were prepared as previously described I. Thyroid cells (1 5 • 107) were incubated in Earle's balanced salt solution, pH 7.4, in the presence of 0.05/~M iodide labelled with 1-5/~Ci 131I, for 2 h at 37 ~ with air as the gas phase and under constant shaking (60 cycles/rain). Iodide trapping, expressed in terms of 1311-C/M ratio: the ratio between intracellular and medium labelled iodide concentration, was determined in the presence of 2 mM methimazole according to Rodesch and Dumont:. Iodide organification was assessed by measurements of 13q-iodide incorporation into acid-insoluble material (mainly iodoproteins). Cell homogenates were supplemented with 0.1 ml 0.2 mM NaI and 0.1 ml 1% (w/v) bovine serum albumin and proteins were precipitated with 5~ (w/v) trichloracetic acid. The 1500• g pellet was washed with 5% trichloracetic acid and counted for radioactivity. Cyclic AMP was assayed as previously described 3. Thyrotropin (TSH),N6,O2'-dibutyryl-adenosine 3':5' monophosphate (db cAMP) and 4-hydroxybenzoic acid methyl ester were obtained from Armour (Kankakee, USA), Sigma (St. Louis, USA) and Organon (France), respectively.