Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function disturbances (stenosis or dyskinesia) may prevent normal bile flow and thus enhance the probability of common bile duct (CBD) stone formation. Previously we have shown that there is an increased prevalence of diagnosed hypothyroidism in CBD stone patients, compared with gallbladder stone patients or age-, sex-, and hospital-admission-adjusted controls. The present study was done to test the hypothesis that thyroxine directly effects the SO. The specificity of the effects of thyroxine were studied by comparing with triiodothyronine (T3), progesterone, cortisone, estrogen, and testosterone. For ex vivo studies three or four successive 1 to 1.5-mm SO rings were prepared from each pig and placed between two hooks in oxygenated physiologic salt solution at 37 degrees C. SO contraction was measured with isometric force displacement transducers and registered on a polygraph. Each SO ring was stimulated with KCl (125 mM), acetylcholine (ACh; 10 or 100 microM) and histamine (Hist; 10 or 100 microM) with and without thyroxine (10(-10) or 10(-8) M), T3 (10(-9) or 10(-7) M), progesterone (1 microM), cortisone (1 microM), estrogen (1 microM), or testosterone (1 nM) in the medium. KCI, ACh, and Hist induced strong contractions in the SO rings. The addition of thyroxine did not influence significantly the KCl-induced contractions, but the ACh- and Hist-induced contractions decreased by a mean of 37-44% (P < 0.001) and 54-56% (P < 0.001), respectively, as compared to the contractions without thyroxine. Triiodothyronine had a similar inhibitory effect to thyroxine, whereas cortisone, estrogen, and testosterone had no effect. Progesterone decreased the KCl-, ACh-, and Hist-induced SO contractions. In conclusion, physiological concentrations of thyroxine have an inhibitory effect on receptor-mediated ACh and Hist, but not on the nonspecific KCl-induced SO contraction ex vivo. The inhibitory effect is similar in thyroxine and triiodothyronine. Of the steroid hormones, only progesterone nonspecifically ameliorates SO contractions ex vivo. Because the effect of thyroxine on the SO is prorelaxing, the lack of thyroxine may result in an increased tension of the SO.