The respiratory control system is subject to considerable developmental plasticity. Perturbations during vulnerable periods of development can induce persistent maladaptive changes. Exposure to intermittent hypoxia (IH) is a common feature of several neonatal respiratory disorders, such as apnoea of prematurity. It has been established that chronic intermittent hypoxia (CIH) induces muscle dysfunction in adult animal models of sleep-disordered breathing. Any impairment in respiratory muscle function may have detrimental effects on respiratory performance and could exacerbate conditions characterised by IH. The major aims of this study were to determine the long-term effects of CIH, during development, on respiratory muscle function and basal breathing. Litters of Wistar rats, together with their dams, were placed from birth or postnatal day 7 in hypoxia chambers. The CIH litters received alternating cycles of 90 sec hypoxia (5% O2 at the nadir) and 210 sec normoxia for 8hr/day for 7 days. Sham litters were exposed to circulating normoxic gas for 7 days. After gas treatments, ventilation and the frequency of apnoeas were measured in sham and CIH treated animals using whole-body plethysmography. Following this sternohyoid and diaphragm muscles were excised and functional properties were examined in vitro. Littermates from sham and CIH groups were returned to normoxia for 21 days, after which ventilation and respiratory muscle function were studies. (n=8 all groups) CIH treatment significantly decreased peak tetanic force in sternohyoid (4.2±0.8 vs. 1.6±0.3 N/cm2 ; sham vs. CIH, P=0.009, Student’s t test) and diaphragm (12.5±1.2 vs.8.0±0.7 N/cm2 , P=0.006) muscles from PD7 rats, but had no effect on PD14 respiratory muscles. CIH increased minute ventilation (209±21 vs. 261±19 ml/min/100g, P=0.09) and apnoea index (9.3±1.9 vs. 14.0±2.3 n/hr, P=0.0674), but these changes did not reach statistical significance. The CIH-induced negative inotropic effects on PD7 respiratory muscles persisted into early adulthood following recovery in normoxia, in sternohyoid (12.9±0.7 vs. 11.0±0.6 N/cm2 , P=0.0685), but not diaphragm muscles. There was no long-lasting effect of CIH on normoxic ventilation or apnoea index. We conclude that early neonatal life represents a particularly vulnerable period for IH-induced respiratory plasticity. The combination of CIH-induced respiratory muscle weakness and increased susceptibility to apnoeas could have significant implications for respiratory performance in infants with immature respiratory control systems. Upper airway dilator, but not diaphragm, muscle dysfunction persisted into early adulthood, this mismatch in respiratory muscle performance could increase the risk of airway collapse in vivo. This is of clinical significance as episodic hypoxia could have detrimental long-term consequences for respiratory homeostasis later in life.