Serum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 micrograms at intervals of 4 weeks to a total of 200 micrograms daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1.35 + 0.23FT4, r = 0.916, P less than 0.001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0.195 square root TT4, (r = 0.936, P less than 0.001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 micrograms of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = -0.022 + 0.0027TT4, r = 0.921, P less than 0.001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r = 0.927, -0.917 and -0.900 respectively). These correlations were significantly better (P less than 0.05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised.(ABSTRACT TRUNCATED AT 250 WORDS)