Mature rats were dosed with T3 by different routes and dose-levels at either 0.1 mg/kg for 14 days s.c. (Group A), 1 mg/kg for 3 alternative days i.p. (Group B), 5 mg/kg for 14 days p.o. (Group C), or with propylthiouracil (PTU 50 mg/day for 14 days p.o.-Group D). Measurement of cerebellar and striatal NA+,K+-ATPase activities showed that whereas Groups A, B and D were unaffected when compared with controls, there were 35-70% increases respectively in the activities of both molecular forms of the enzyme, alpha(+), high ouabain affinity, and alpha, low ouabain affinity, in Group C rat brains at the highest dose of T3 tested. Kidney Na+,K+-ATPase activity was also elevated (67% increase) in this group of animals showing significant changes in renal medullary tissue only. Acute elevation of brain dopamine levels by administration of an MAOI plus L-DOPA (50 mg/kg, 60 min) significantly elevated (20% increase) the activities of both molecular forms of Na+,K+-ATPase in corpus striatum. Treatment with L-tryptophan (50 mg/kg, 60 min) failed to produce any changes in the striatal activities. The possible relationship of increases in enzyme activities with T3 and increased brain monoamine function is discussed. Both plasma free T4(FT4) and total T4(TT4) were markedly depressed in all T3-treated rats. Although hypothalamic thyrotropin releasing hormone (TRH) concentrations were unaltered by any of the T3 treatments, pituitary thyroid stimulating hormone (TSH) concentrations were greatly diminished and it is thought that this may reflect a direct effect of T3 on TSH synthesis.