To evaluate the effect of dietary fiber supplements on levothyroxine (T4) bioavailability in hypothyroid patients, dietary fiber-containing supplementation was withheld from patients requiring disproportionately high doses of T4, in whom a dietary history revealed ingestion of a dietary fiber supplement. The dose of T4 was maintained at a constant level. Serum thyrotropin (TSH) was assessed before and after removal of the dietary fiber supplements. T4 requirements, reflected by either decreased serum TSH or by decreased T4 dose, was observed in conjunction with decreased dietary fiber intake compared with T4 requirement during increased dietary fiber intake. In vitro experiments carried out to determine the mechanism of interaction between dietary fiber and T4 revealed dose dependent, nonspecific adsorption of levothyroxine by wheat bran. These results indicate a decrease in T4 bioavailability by dietary fiber through a mechanism involving nonspecific adsorption of T4 to dietary fibers. Increased intake of dietary fiber may account for the need for larger than expected doses of T4 in some hypothyroid patients.