The concentration of ouabain binding sites (OBS), a measure of the abundance of sodium/potassium-dependent ATPase (Na/K-ATPase), was measured in cerebral cortex (CC), cerebellum (CBL), brown adipose tissue (BAT), and heart of neonatal rats with congenital hypothyroidism. In euthyroid rats, the concentration of OBS was 50- to 100-fold greater in the nervous tissue than in the nonnervous tissue. Congenital hypothyroidism resulted in a significant reduction in the number of OBS in all four tissues. Although in absolute terms (pmol/mg protein) the reduction was greater in the nervous tissues, in relative terms it was much greater in the nonnervous tissues. The restoration of OBS concentration was much more sensitive to T4 in CC, CBL, and BAT than in heart. In contrast, the response of OBS concentration to T3 in hypothyroid rats was greater in the heart, followed by the BAT and CBL, being minimal in CC. The sensitivity to T4 replacement correlated with the degree of the stimulation of the type II 5'deiodinase (5'D-II) by hypothyroidism, whereas the response to exogenous T3 correlated with the fraction of the tissue T3 that derives from plasma T3 and inversely with the plasma T3 concentration required to saturate 50% of the nuclear receptors as reported in previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)