Changes of nuclear T3 receptors during brain maturation were studied in normal and hypothyroid rats. In normal rats, the higher receptor concentration present in the neonatal period (0.35 +/- 0.04 ng T3/mg DNA) decreased at the age of 14 days (0.25 +/- 0.02 ng T3/mg DNA), and remained at this level thereafter to 35 days of age (0.25 +/- 0.03 T3/mg DNA). In contrast, hypothyroid rats showed a significantly higher concentration than that found in an age-matched control group at the age of 14 days (0.38 +/- 0.07 ng T3/mg DNA), and maintained this level up to 35 days of age (0.37 +/- 0.03 T3/mg DNA). The binding affinity was similar in both groups and throughout maturation (mean +/- SD in normal groups; 1.9 +/- 0.3 X 10(10)M-1, in hypothyroid groups: 1.7 +/- 0.2 X 10(10)M-1). Plasma T3 concentrations showed changes reciprocal to those in the binding capacity of T3 receptors. These results indicate that nuclear T3 receptors in rat brain mature by the age of 14 days, in association with a decrease in binding capacity, and this process seems to be T3-dependent. The physiological role of the high concentration of T3 receptors observed in neonatal and hypothyroid rat brain during development is at present not clear.