Permissive hypercapnia, a strategy allowing high Pa(CO2), is widely used by neonatologists to minimize lung damage in ventilated very low birth weight (VLBW) infants. While hypercapnia increases cerebral blood flow (CBF), its effects on cerebral autoregulation of VLBW infants are unknown. Monitoring of mean CBF velocity (mCBFv), Pa(CO2), and mean arterial blood pressure (MABP) from 43 ventilated VLBW infants during the first week of life was performed during and after 117 tracheal suctioning procedures. Autoregulation status was determined during tracheal suctioning because it perturbs cerebral and systemic hemodynamics. The slope of the relationship between mCBFv and MABP was estimated when Pa(CO2) was fixed at 30, 35, 40, 45, 50, 55, and 60 mm Hg. A slope near or equal to 0 suggests intact autoregulation, i.e. CBF is not influenced by MABP. Increasing values >0 indicate progressively impaired autoregulation. Infants weighed 905 +/- 259 g and were 26.9 +/- 2.3 wk gestation. The autoregulatory slope increased as Pa(CO2)) increased from 30 to 60 mm Hg. While the slopes for Pa(CO2) values of 30 to 40 mm Hg were not statistically different from 0, slopes for Pa(CO2) > or = 45 mm Hg indicated a progressive loss of cerebral autoregulation. The autoregulatory slope increases with increasing Pa(CO2), suggesting the cerebral circulation becomes progressively pressure passive with hypercapnia. These data raise concerns regarding the use of permissive hypercapnia in ventilated VLBW infants during the first week of life, as impaired autoregulation during this period may be associated with increased vulnerability to brain injury.