The influence of varying thyroid metabolic states, induced by thyroxine (T4) application, upon type I T4 deiodinating activity has been assessed in the rat liver. A series of 18 rats was thyroidectomized and treated with T4 at various doses, ranging from 0 to 50 micrograms/kg b.w. Microsomal T4 to triiodothyronine (T3) deiodinating activity (5'DA) and T4 to reverse T3 (rT3) deiodinating activity (5DA) as well as cytosolic non protein bound thiol content (NP-SH) were determined in the liver; concentrations of T4, T3, and rT3 were measured in the serum. In the experimental rats, T4 serum concentrations ranged from 1.3 micrograms/dl to 15.6 micrograms/dl (controls, 5 +/- 0.2 micrograms/dl, mean +/- SEM), T3 varied between 33 ng/dl and 150 ng/dl (91 +/- 3 ng/dl), and rT3 between 2 ng/dl and 25 ng/dl (7 +/- 2 ng/dl). Relating T4 to T3 serum levels, a curvilinear relationship (power function, r = 0.94, p less than 0.001), as described previously in man, was confirmed in the rats, as was the linear relationship between T4 and rT3 serum levels (r = 0.75, p less than 0.001). Individual 5'DA increased by more than fourfold, from 531 pg/mg.min to 2,234 pg/mg.min (controls, 1,419 +/- 67 pg/mg.min), when passing from low to high T4 serum values. The increase in 5'DA was steeper in the low T4 range, while it was progressively flattened under T4 levels above the controls' range. The particular changes in 5'DA can be illustrated by calculating the ratio of 5'DA and T4 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)