Sodium nitroprusside (SNP) spontaneously breaks down in solution to produce nitric oxide (NO). In many cell types NO stimulates cytosolic guanylate cyclase activity. A recent report suggests that NO may regulate secretion from endocrine organs. It has been demonstrated that SNP used as a source of NO increases cGMP levels in thyroid cells A reduction in iodide uptake and no change in hormone secretion were observed in bovine and human thyroid cells respectively. The aim of this work was to further study the effect of SNP on the uptake, transport and organification of iodide in TSH-stimulated bovine thyroid cells. In primary culture the morphology of the cells was also observed. Iodide uptake and organification were measured after 60 min of cell incubation at 37 C with 1 uCi Na131I (carrier free). Uptake (organified plus nonorganified iodide) was determined by measuring total intracellular radiactivity incorporated into cells and iodide organification by protein-bound 131I after precipitation with trichloroacetic acid. Values were expressed as cpm/pg DNA. Iodide transport was measured as the iodide concentrating activity of cells in the described conditions plus 0 1 pmol/L KI and 1 mmol/lL methylmercaptoimidazole (MMI). Iodide diffusion was measured by adding 1 mmol/L KCl04. Values were expressed as the ratio of cpm per mg DNA of cells/cpm per mL medium. As variable iodination values among cultures were obtained results were expressed as percent of TSH value. A strong dose-dependent inhibition of the three parameters assayed was observed. At longer periods a sustained inhibition on the progressive increase of iodide uptake induced by TSH was also obtained. Uptake values with 1 mU/mL TSH  (cpm/ug DNA MEAN +/-  SD) were 24 h  39 +/- 4, 48h 28 +/-8, 72h 80 +/-36, 96h 185 +/-48. Values with SNP (100 umol/L were (% of TSH value) 16+/-10*; 5 +/-2*; 5+/-1* and 3 +/-3*, respectively (* = P < 0 001; n=6). The reduction of iodide uptake appears to be due to an impairment of both iodide transport and organifcation. The inhibition of iodide organification could not be totally attrIbutable to the reduction in the iodide transport since this reached lower inhibition levels. Morphological changes compatible with cell dedIfferentiation were induced by SNP. In a dose-dependent fashion, SNP produced spreading out and loss of follicular formations with the appearance of monolayers of flattened cells. Trypan blue exclusion staining of SNP treated cells showed that cell viability was similar to that in untreated cells. We conclude that  SNP exerts some dedifferentiating effects on primary bovine thyroid cells mainly evidenced by a reduced iodide organification.