Direct information concerning the fetal development of bilirubin glucuronidation in man has been lacking. Both the activity of the conjugating enzyme, bilirubin UDP-glucuronyltransferase (UDPGT) and the availability of the substrate, UDP-glucuronic acid (UDPGA) may affect hepatic bilirubin glucuronidation. Assays of UDPGT and UDP-glucose dehydrogenase (UDPGD) were performed in the livers of dead aborted human fetuses and the results were compared with values obtained in normal adults. Hepatic UDPGT activity (unit = μg bilirubin conjugated/gm liver/hr in 2 fetuses, aged 17 and 22 weeks was 140 and 220 units, respectively and in 7 fetuses, aged 11-19 weeks was less than 100 units (normal adult = 600-2,000 units). Hepatic UDPGD activity (unit = ηmoles UDPGA formed/100gm liver/min.) in 10 fetuses, aged 10-18 weeks, ranged from 7.7 - 15.0 units (mean ± SEM = 11.7 ± 8.0) and in 8 normal adults ranged from 26.3 - 49.2 units (mean ± SEM = 38.1 ± 3.0) (p<0.001). These data show that the in vitro hepatic formation of bilirubin glucuronide and UDPGA is markedly reduced in the human fetus in the first half of gestation compared to normal adults. The relation of these findings to in vivo hepatic bilirubin metabolism and glucuronide conjugation in general in the human fetus and newborn remains to be determined.