Chemical sympathectomy was achieved in 8 fetal lambs in utero by daily intravenous infusion of 6-hydroxydopamine (6HD). The dose was increased progressively until a cumulative dose of 60-70 mg/kg was reached. Adequacy of adrenergic denervation was verified by the lack of any cardiovascular response to intravenous tyramine. Plasma catecholamine concentrations in normoxemic, sympathectomized fetuses were slightly higher than controls. After 6HD norepinephrine (NE) = 313 +/- 73 pg/ml (mean +/- SEM) compared to control values of 259 +/- 25 pg/ml (NS). Epinephrine (E) = 39 +/- 15 pg/ml in 6HD fetuses versus 21 +/- 4 pg/ml in controls (NS). There was a small but significant increase in arterial blood pressure (BP) (p less than 0.05), while heart rate (HR) was unchanged. Following hypoxemia, control animals demonstrated a profound increase in plasma NE (2,461 +/- 419 pg/ml) and E (2,017 +/- 749 pg/ml) along with hypertension and bradycardia. Sympathectomized fetuses maintained the NE response to hypoxemia (NE = 1,550 +/- 261 pg/ml), but the peak E response (E = 244 +/- 42 pg/ml) was significantly reduced (p less than 0.05). HR and BP responses were similar to control animals. Therefore, generalized chemical sympathectomy in the fetal lamb in utero is useful in evaluating sympathoadrenal modulation of the fetal cardiovascular system. Despite the lack of neurosympathetic activity, the sympathectomized fetus is capable of maintaining appropriate BP responses to hypoxemia by the direct effect of hypoxemia on adrenal medullary NE release.