In order to determine the effects of the administration of diphenylhydantoin (DPH) on various parameters of thyroid function, serum samples from 47 male adults receiving therapeutic doses of DPH and 45 euthyroid control subjects were analyzed for total thyroxine (T4) and an index of free T4 concentration, using both a competitive protein-binding assay (CPBA) and a solid-phase radioimmunoassay (RIA), total 3,5,3′-triiodothyronine (T3), 3,3′,5′-triiodothyronine (reverse-T3, rT3), and TSH, each measured by specific RIA. Mean total T4 by both methods was depressed in the DPH group to 0.78 of the control level. Free T4 Index by RIA was decreased on the average in DPH-patients exactly in proportion to the depression in total T4. By the CPBA, the difference between two groups in Free T4 Index was less marked but still significant (DPH/controls = 0.86, p < 0.01). The concentrations of total T3 were virtually identical in the DPH and the control groups. The average T3 T4 ratio was significantly higher in the DPH patients than in the controls (0.0178 versus 0.0132, p < 0.001). Serum rT3 was depressed by DPH-treatment in approximately the same proportion to the decrease in total T4. None of the DPH-patients had an elevated serum TSH. The above findings are interpreted as indirect evidence in support of the view that DPH stimulates T4 metabolism, particularly the conversion of T4 to T3. The normal level of free T3 may help to maintain a euthyroid state in spite of the decrease in free T4. The data also define the euthyroid" ranges for total and free T4 levels by these methods in patients receiving DPH. © 1979."