The effects of bile acids on iodide uptake and DNA synthesis were studied in cultured porcine thyroid cells. All five bile acids, which are commonly found in serum, chenodeoxycholic acid (CDCA), cholic acid (CA), deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) dose-dependently inhibited both basal and TSH-induced iodide uptake at concentrations of 25-250 microM. Since CDCA is one of the two major primary endogenous bile acids, were studied mainly the effects of CDCA. The inhibitory effect of CDCA was detected after 24 h treatment of thyroid cells, and was dependent on the time of exposure up to 72 h. Treatment of thyroid cells with CDCA for 72 h inhibited cAMP production stimulated by 50 mU/L TSH or 0.5 mg/L forskolin and also inhibited iodide uptake induced by 0.5 mM 8-bromo cAMP or 0.5 mg/L forskolin. These results suggest that CDCA inhibits iodide uptake by decreasing cAMP production as well as post-cAMP generation. Bile acids except LCA stimulated [3H]thymidine incorporation into the thyroid cells by itself, indicating that the inhibitory effect of bile acids on iodide uptake is not due to cytotoxic effect. In conclusion, these findings suggest that the direct inhibition of thyroid function by bile acids might cause hypothyroidism in chronic liver disease.