The effects of chronic mild hypoxemia on the binding of angiotensin receptors in selected brainstem nuclei and reflex responses were studied in fetal sheep. Fetal and maternal catheters were placed at 120 days' gestation and animals received intratracheal maternal administration of nitrogen (n=16) or compressed air in controls (n=19). Nitrogen infusion was adjusted to reduce fetal brachial artery PO₂ by 25% during 5 days. Spontaneous baroreflex sensitivity and spectral analysis of the pulse interval were analyzed during the 5 days hypoxemia period using 90 min of daily recording. Brains of control and hypoxemic animals were collected and brainstem angiotensin receptor binding studied by in vitro autoradiography at 130 days of gestation. After 5 days of hypoxemia some animals in each group were submitted to one complete umbilical cord occlusion during 5 minutes. [¹²⁵I]-Sarthran binding showed that chronic mild hypoxemia significantly increases AT₁, AT₂ and Ang-(1-7) angiotensin receptor binding sites in NTS and dmnX (p<0.05). Hypoxemia induced lower baroreflex sensitivity and a higher LF/HF ratio in the fetus, consistent with a shift from vagal to sympathetic autonomic cardiac regulation. Cord occlusion to elicit a chemoreflex response induced a greater bradycardic response in hypoxemic fetuses (slope of the initial fall in heart rate; 11.3±1.9 vs. 6.4±1.2 bpm•sec^-1, p<0.05). In summary, chronic mild hypoxemia increased binding of angiotensin receptors in brainstem nuclei, decreased spontaneous baroreflex gain and increased chemoreflex responses to asphyxia in the fetus. These results suggest hypoxemia-induced alterations in brainstem mechanisms for cardiovascular control.