Brown adipose tissue (BAT) is the major thermogenic organ of the human neonate. To determine whether it is also active in the peripheral conversion of T4 to T3, as shown in several animal species, interscapular BAT from 13 newborns of 25-40 weeks gestational age who survived 4 days, at most, was investigated. BAT was found to contain significant amounts of the mitochondrial uncoupling protein (UCP), the rate-limiting component of heat production. The specific content of UCP increased from 29.4 +/- 3.3 to 62.5 +/- 10.2 pmol/mg protein between 25 and 40 weeks of gestation, respectively, and the UCP/F1-ATPase molar ratio, a sensitive marker of brown fat differentiation, increased similarly. BAT was also found to contain iodothyronine 5'-deiodinase (5'D), which appears to be a type II enzyme, based on high affinity for T4 (Km, 2.9 nmol/L) and insensitivity to propylthiouracil (10% inhibition by 1 nmol/L). 5'D was active by 25 weeks gestation, and the specific activity increased from 116 +/- 15 to 417 +/- 46 fmol/h.mg protein during the period examined. The development of 5'D activity was similar to the changes in UCP content; both exhibited a major increase before 32 weeks gestation. The results indicate that thermogenic function and 5'D activity develop in human BAT rather early, during the first half of the last trimester of gestation. The activities of 5'D in human BAT are comparable with 5'D activities found in animal BAT stimulated during the perinatal period, by cold exposure, or by increased cAMP levels.