We have investigated the impact of chronic restriction of placental function on circulating catecholamine concentrations and responses to the indirectly acting, sympathomimetic amine, tyramine, in the fetal sheep in late gestation. In 10 ewes, endometrial caruncles or placental placentation sites were removed before conception (placental restriction (PR) group). Fetal sheep in the PR group were hypoxemic throughout late gestation and growth-restricted(3.02 ± 0.35 kg) when compared with control fetal sheep (4.30 ± 0.29 kg;n= 8) at 140 d of gestation. Fetal plasma concentrations of noradrenaline and adrenaline were higher (p< 0.05) in the PR(7.06 ± 3.17 pmol/mL and 2.89 ± 2.01 pmol/mL, respectively) than in the control group (3.55 ± 0.54 pmol/mL and 1.30 ± 0.48 pmol/mL, respectively) throughout late gestation. Plasma noradrenaline, but not adrenaline concentrations, increased significantly between 110 and 140 d of gestation in both the PR and control group, and there was a significant inverse relationship between plasma noradrenaline and arterial Po2in the PR and control groups (plasma noradrenaline = 12.34 - 0.40 Po2). In the PR group, plasma noradrenaline increased (p< 0.05) after tyramine infusion from 4.51 ± 1.28 pmol/mL to a peak of 19.40 ± 3.56 pmol/mL. In the control group, noradrenaline increased from 2.08 ± 0.30 pmol/mL to a peak of 12.23 ± 1.67 pmol/mL after tyramine infusion. There was no difference, however, in the maximal proportional changes in plasma noradrenaline concentrations in the PR (319 ± 55%) and control(449 ± 100%) groups after tyramine. We conclude that the most likely source of the increased plasma catecholamines in the PR group is enhanced catecholamine synthesis and secretion from developing sympathetic neurons.