Bacterial endotoxin LPS induces the expression of multiple genes including nitric oxide (NO) synthase. LPS is present in blood in certain infectious processes. This study analyzed the LPS action on the expression of thyroid specific genes and the iodide uptake in TSH (500m IU/ml)-stimulated FRTL-5. The Tg and TPO mRNA expression (Northern-blot) was decreased by LPS (0.01-1m g/ml): (absorbance ratio mRNA/18S rRNA; arbitrary units): Tg: Basal(B): 0.45± 0.09; Control(C): 1.00± 0.03; LPS (m g/ml) 0.01: 0.59± 0.04**, 0.05: 0.55± 0.05**, 0.1: 0.66± 0.09*, 1: 0.79± 0.09. TPO: B: 0.51± 0.07; C: 1.00± 0.06; LPS (m g/ml) 0.01: 0.64± 0.03**, 0.05: 0.61± 0.03**, 0.1: 0.61± 0.08*, 1: 0.69± 0.14 (n=3; **p<0.01; *p<0.05 vs C). A non significant reduction in the sodium-iodide transporter (NIS) mRNA expression was induced by LPS. The iodide uptake (¹³¹I) was increased by LPS (0.01-10m g/ml) in a concentration-dependent manner (maximum at 0.1m g/ml): (cpm/m g DNA; 48h): B: 91.2± 11.4; C: 593.6± 26.6; LPS (m g/ml) 0.01: 1161.9± 110.6***; 0.05: 1103.2± 96.1***; 0.1: 1532.6± 148.6***; 1: 1071.5± 212.0**; 5: 972.4± 156.2**; 10: 899.2± 123.9** (n=14; ***p<0.0001; **p=0.01 vs C). This effect was time-dependent (highest value at 48h). In contrast, LPS inhibited iodide uptake at higher concentrations: (% of control; 48h): C: 100± 4%; LPS (m g/ml) 100: 144± 36%, 500: 44± 10%***, 1000: 21± 3%*** (n=9; ***p<0.0001 vs C). LPS (0.01-1000m g/ml; 48h) did not induce NO generation (nitrite accumulation). Results (mean± SEM) were analyzed by ANOVA and Student t test. In conclusion, these findings revealed that LPS differentially influence thyroid specific gene expression and iodide uptake. A mediation of NO in the LPS action is unlikely. The changes induced by LPS on parameters of thyroid hormone biosynthesis support a potencial ability of the endotoxin to alter the thyroid function.