We have studied T3 sulfate (T3S) levels, blindly, in coded plasma samples from 21 normal and 3 hypothyroid fetuses at different stages of gestation (19-42 weeks). Fetal plasma samples were obtained by cordocentesis. T3S was detectable in all samples studied, with values ranging from 50-294 (mean +/- SD, 130 +/- 62 pmol/L). Plasma T3S was low (< 45 pmol/L) in all 4 normal adult control subjects studied simultaneously; serum T3S ranged from less than 20 to 130 in another set of 18 control subjects (mean +/- SD, 63 +/- 32 pmol/L). Fetal T3S values were positively correlated with gestational age (r = 0.43; P < 0.05), but not with free T4 (FT4), FT3, or TSH values. In the 3 hypothyroid fetuses at 31, 38, and 40 weeks gestation, respectively, plasma TSH was elevated (26, 98, and 24 mU/L, respectively), FT4 was low (10, 6.7, and 7.5 pmol/L, respectively), and FT3 was normal or high (3.2, 8.2, and 2.2 pmol/L, respectively). However, T3S values in hypothyroid fetuses (88, 133, and 252 pmol/L, respectively) were similar to those in normal fetuses at corresponding gestational ages. We conclude that 1) T3S is detectable in fetal circulation from at least 19 weeks gestation, and its concentration increases with fetal-age; 2) plasma T3S concentrations in the fetus at 19-40 weeks gestation are at least comparable to but generally higher than those in the adult; and 3) plasma T3S levels in hypothyroid fetuses are similar to those in normal fetuses. Recent studies demonstrating the ability of some fetal rat tissues (e.g. cerebral cortex) to desulfate T3S to T3 have suggested a possible role of T3S as a source of T3. Normal T3S in fetal hypothyroidism suggests that T3S may contribute to attenuation of the effects of hypothyroidism during intrauterine life.