The ventilatory response to hypoxia matures postnatally in mammals due partly to resetting of the carotid bodies (Koch & Wendel, 1968). In the adult, the carotid bodies respond to a hypoxic stimulus by exponential increases in nerve discharge, resulting in an increase in ventilation (Eden & Hanson, 1987). In the neonate, before resetting, this response is greatly blunted. Exposure of the fetus or neonate to a suboptimal environment induces adaptive responses that may persist after the stimulus is removed and may even be present in adult life – this has been termed fetal programming (Barker, 1995). We have used chronic hypoxia in utero test whether fetal programming affects maturation of the respiratory responses to hypoxia in the rat. Female Wistar rats were mated in normoxia and housed in a chamber at 12% O₂ between days 10 and 20 of gestation to induce chronic hypoxia in utero (CHU). After day 20, the dams were housed in normoxic conditions to give birth and rear the pups. All experiments were performed on male offpsring (body weight CHU; 335±5g, n=17 and normoxic (N) controls; 256±9g, n=6). In experiments on Saffan-anaesthetised rats, the trachea was cannulated in order to induce 5 min periods of graded levels of hypoxia (12%, 10%, 8% O₂). Arterial blood gases were measured from the brachial artery. Measurements of respiratory frequency (R_f) and tidal volume (V_t – normalised for body weight) were made by spirometry. Experiments performed on the isolated carotid body (Landauer et al, 1995) measured carotid sinus nerve discharge in response to changing superfusate PO₂ at two constant levels of perfusate PCO₂. No difference in P_aO₂ was measured between CHU and N rats. Normoxic minute ventilation (V_e) was significantly lower in CHU rats (0.38±0.03 vs 0.56±0.04 ml/min/g body weight; mean±s.e.m.), with both R_f and V_t being lower. Graded hypoxia showed increases in V_e in both groups but were significantly less pronounced in CHU rats due to smaller increases in R_f (increase at 1min of 10% O₂ of 17±3 vs 27±3 breaths/min in N rats). Carotid sinus nerve discharge was similar in both N and CHU rats at higher superfusate PO₂ levels (PO2=400mmHg). Discharge from the CHU carotid bodies increased in response to hypoxia but was significantly depressed compared to N (3.5±0.9 vs 13.7±4.4Hz at PO₂=100mmHg, PCO₂=40mmHg). CHU does provide a programming stimulus in the maturation of respiratory control mechanisms. This is reflected by smaller changes in carotid body nerve discharge in response to hypoxia and hypercapnia. In the whole animal, this is also manifest by smaller increases in R_f in response to hypoxia.