Three commercial kit methods for the estimation of free thyroxine (FT4) (Clinical Assays, Corning Medical, Damon Diagnostics) were evaluated. The effects of changes in thyroxine-binding globulin (TBG) and FT4 concentrations in these systems were assessed. Measurements were made in serum samples from hyperthyroid, hypothyroid, and euthyroid patients with different TBG concentrations, and results were correlated with functional thyroid status. The Clinical Assays and Damon Diagnostics assays were found to be essentially independent of binding-protein concentration effects and responded appropriately to changes in FT4 concentration. The method of Corning Medical does not measure FT4 directly but yields an FT4 index calculated from a TBG-dependent T4 uptake and the total T4 concentration. This corning index yields falsely elevated results in patients with marked elevation in TBG concentration.