To evaluate the diagnostic value of subject-based reference values in thyroid function tests, we compared intra-individual and inter-individual variation. Five specimens were collected over a period of 2 weeks from each of 47 normal subjects, 29 women and 18 men, aged 20-47 yrs. T-4, FT4, T-3, and FT3 were assayed by RIA, and TSH by a sensitive immunoradiometric assay. One-way ANOVA for each test was statistically significant for a main subject effect, indicating that the subjects differed in their personal mean values for the thyroid function tests (T-4, P<0.01; FT4, P<0.05; T-3, P<0.01; FT3, P<0.05; TSH, P<0.01). The ratio value (intra- over inter-individual variation) was T-4, 0.41; FT4, 0.60; T-3, 0.53; FT3, 0.63; TSH 0.36. The data indicate that conventional reference values are insensitive when compared to subject-based reference intervals in assessing the thyroid status of a given subject. Reactivity of the thyroid to the stimulation of endogenous TSH was assessed by the ratio Delta FT3/Delta TSH in TRH stimulation tests. 4 positive correlation between basal FT3 and Delta FT3/Delta TSH (r=0.566, P<0.05) indicates that the thyroid with higher reactivity to TSH secretes more daily thyroid hormone. Negative correlation between basal TSH and Delta FT3/Delta TSH (r=-0.536, P<0.05) means that a subject with lower reactivity of the thyroid needs a higher basal TSH level to compensate. The thyroid reactivity to TSH may be an important determinant for the individuality of the pituitary-thyroid axis.