Hepatic bilirubin uridine diphosphate glucuronyl transferase (UDPG-T) activity was 0.14 and 0.22 units in two fetuses aged 17 and 22 weeks, respectively, and less than 0.1 unit in 15 fetuses, aged 8--19 weeks compared to 0.68--1.99 units in 21 normal adults. Hepatic uridine diphosphate glucose dehydrogenase (UDPG-D) activity in 14 fetuses, aged 8--18 weeks, ranged from 6.2--15.0 units (mean = 11.3 +/- 0.7) compared to 28.8--49.2 units (mean = 39.6 +/- 2.5) in eight normal adults (P less than 0.001). There was no correlation between UDPG-D activity and gestational age. The hepatic UDPG-D activity was 16.5 units in a 33-day-old full term, female infant, 42.4 and 24.3 units in two 2-year-old infants, respectively, and 24.3 units in a 5.5-year-old child. In three human fetuses, the apparent Km UDPG was 0.54 x 10(-4) M. Thus, both hepatic bilirubin UDPG-T and UDPG-D activity are markedly reduced in the human fetus during the second trimester of gestation. Retarded development of hepatic UDPG-D may extend beyond the first month of life.