The effects of placental lactogen on glycogen metabolism have been studied in cultured hepatocytes from 20-day-old fetal rats. Ovine placental lactogen (oPL; 2, 5, 10, and 25 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen and total cellular glycogen content after 4 h of incubation but had no effect on glycogen degradation. Half-maximal stimulation occurred with an oPL concentration of 3 micrograms/ml. In contrast, human placental lactogen had no effect on [14C]glucose incorporation into glycogen. Ovine growth hormone (50 and 100 micrograms/ml), rat growth hormone (20, 40, and 100 micrograms/ml), and ovine prolactin (10, 40, and 100 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen, but the potencies of these hormones were only 10-20% of that of oPL. Insulin (20 nM) stimulated [14C]glucose incorporation into glycogen, whereas glucagon (0.5 and 20 nM) inhibited [14C]glucose incorporation into glycogen and increased glycogen degradation. Our findings suggest that oPL may have direct insulin-like effects on carbohydrate metabolism in the fetus and that oPL may contribute to the accumulation of fetal liver glycogen that occurs in late gestation.