Objective: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT 4 ) combination in each individual. Subjects and methods: Twenty-one healthy volunteers (nine males and 12 females; mean age 60 years, range 51-74) were randomized to receive at 2300 h with 2-week intervals a single dose of placebo, 125 mg T 4 and 250 mg T 4 (arm 1, nZ10), or placebo, 25 mg triiodothyronine (T 3 ) and 50 mg T 3 (arm 2, nZ11). Blood samples were taken in the morning (0800-1100 h) before and following the administration of the drug for the assessment of TSH, FT 4 and T 3 . Results: Intra-and inter-individual variation and the individuality index of the four baseline serum samples were respectively 21.6%, 41.9% and 0.52 for TSH; 9.9%, 16.5% and 0.60 for FT 4 ; and 9.3%, 16.0% and 0.58 for T 3 . Substantial differences existed in the location of individual working points within the reference range. T 4 administration increased FT 4 (but not T 3 ) and decreased TSH, resulting in a log-linear relationship (log TSHZ1.50-0.059!FT 4 , P!0.05) for the whole group. T 3 administration increased T 3 and decreased TSH (but not FT 4 ), resulting in a log-linear relationship (log TSHZ0.790-0.245!T 3 , P!0.001) for the whole group. Log-linear relationships were not always significant when assessed for each subject separately. Conclusion: Individuality indices of TSH, FT 4 and T 3 are all %0.6, thereby limiting the usefulness of the population-based reference values. Accurate assessment of individual setpoints of the HPT axis was not possible with the applied single doses of T 4 or T 3 , and will require either prolonged administration or higher single doses of thyroid hormone.