It is unknown whether the JAK / STAT / SOCS-3 intracellular signaling pathway plays a role in tissue growth and metabolism during fetal life. We have investigated whether there is a differential profile of SOCS-3 expression in the liver and perirenal adipose tissue during the period of increased fetal growth in late gestation and the impact of fetal growth restriction on SOCS-3 expression in the fetal liver. We have also determined whether basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is regulated by endogenous fetal prolactin. The abundance of SOCS-3 mRNA was higher in the liver than in the pancreas, spleen and kidney of the sheep fetus during late gestation. There was an increase (P < 0.05) in SOCS-3 expression in the fetal sheep liver between 125 d (n = 4) and 145 d (n = 7) gestation and SOCS-3 mRNA expression was lower (P < 0.05) in the liver of growth restricted compared to the normally grown fetal sheep in late gestation. The relative expression of SOCS-3 mRNA in the fetal liver was directly related to the mean plasma PRL concentrations during a 48 h infusion of either a dopaminergic agonist, bromocriptine (n = 7) or saline (n = 5) such that SOCS-3 mRNA expression was lower when plasma PRL concentrations decreased below ~20 ng/ml (y = 0.99 -(2.47/x) + (4.96/x²), r² = 0.91, P < 0.0001, n = 12). There was no relationship, however, between the abundance of phospho-STAT5 in the fetal liver and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased (P < 0001) between 90-91 d (n = 6) and 140-145 d (n = 9) gestation and was not related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed and regulated in a range of key fetal tissues and may play an important and tissue specific role in the regulation of cellular proliferation and differentiation before birth.