INTRODUCTION Pre-term birth, typically defined as birth occurring prior to the 36th week of gestation, has been reported to significantly hamper functional and anatomical development of the respiratory system (1). Prematurely born individuals present reduced cardiopulmonary control, as well as impaired alveologenesis and pulmonary vasculogenesis, leading to inefficient gas diffusion capacity. Either ventilation-to-perfusion mismatch and/or right heart dysfunction have been suggested as potential mechanisms responsible for alteration in respiratory function (2). Recent work from our group has also demonstrated higher oxidative stress in prematurely born adults (3), which may negatively affect both peripheral and central chemosensitivity to hypoxia and hypercapnia, respectively. The aim of this study was to investigate the resting ventilatory responses to normoxic hypercapnia and normobaric hypoxia in prematurely born, but otherwise healthy, adults. METHODS Seventeen pre-term adults (Mean±SD; age, 21±2 years; height, 177±7 cm; body mass, 68.9±7.5 kg; gestational age, 29±3 weeks; gestational weight, 1234±315 g) and fourteen age-matched full-term controls (age, 22±2 years; height, 180±5 cm; body mass, 73.5±5.6 kg; gestational age, 39±2 weeks; birth weight, 3672±499 g) underwent two 5-min resting normoxic hypercapnic periods  (3% CO2 and 6% CO2, respectively), interposed by 5-min ambient air exposure (visit 1). On a second occasion, the participants underwent, again at rest, 4-min of normoxic breathing, before being exposed to 4-min of normobaric hypoxia (FIO2=0.11) (visit 2). Minute ventilation (V̇E), breathing frequency, tidal volume, and end-tidal partial pressure of CO2 (PETCO2), were continuously recorded during both sessions. RESULTS On both occasions, pre-term adults showed lower PETCO2 during rest in normocapnic normoxia than their full-term counterparts (visit 1: 36±4 vs. 39±2 mmHg, p=0.02; visit 2: 36±3 vs. 38±2 mmHg, p=0.04), while no difference was observed in V̇E. During 3% normoxic hypercapnia, PETCO2 increased to a greater extent over the first minute in pre-term, relative to full-term, adults (+11±3% vs. +16±5%, p=0.05). No difference in V̇E was observed between groups while breathing 3% CO2. During 6% hypercapnic exposure, PETCO2 increased similarly in both groups, while V̇E was higher in pre-term compared to full-term adults (30.2±7.5 vs. 23.7±4.5 L/min, p<0.0001). The relative increases in PETCO2 and V̇E during the first minute breathing 6% CO2 were higher in preterm (+31±8% and +64±35%, respectively) compared to full-term (+21±5% and +35±21%, p=0.002 and p<0.04, respectively). During normobaric hypoxia, PETCO2 and V̇E increased from normoxia to a similar extent in both groups, thus maintaining significantly lower PETCO2 in pre-term compared to full-term adults. Interestingly, exposure to normobaric hypoxia resulted in significantly higher breathing frequency among the prematurely born group, relative to their full-term counterparts. CONCLUSIONS These findings support previous evidence on prematurity-induced alterations in pulmonary function which persist into adulthood (1). Pre-term individuals presented a hypocapnic status at rest which may be related to ventilation-to-perfusion mismatch and/or cardiac dysfunction. Moreover, this was the first study showing evidence that pre-term birth is associated with increased chemosensitivity to hypercapnia, but not to hypoxia, compared to full-term birth. These novel findings might suggest that prematurity results in exaggerated central chemosensitivity despite unchanged peripheral chemosensitivity.