We have previously reported reduction in EEG activity in preterm babies after tracheal instillation of Curosurf. To elucidate the cause of EEG depression, we have examined cerebral blood flow (CFB), amplitude-integrated EEG (aEEG), mean arterial blood pressure (MABP) and plasma hypoxanthine (Hx) concentration in a group of preterm babies before and immediately after administration of surfactant. No change occurred in CBF immediately after surfactant treatment despite a significant decrease in MABP. At 60 min after surfactant administration, a significant reduction in CBF occurred (p < 0.05). However, when CBF values were corrected for changes in PaCO2, no reduction in CBF was observed. Mean plasma Hx concentration was 11.6 (SD 7.3) mumol/l before surfactant therapy, which decreased significantly to 8.1 (5.8) mumol/l (p < 0.05) 15-30 min after treatment. No correlations were found between plasma Hx concentration and FiO2, a/A pO2, PaCO2, SaO2, arterial blood pressure, CBF or the degree of EEG depression. This study indicates that EEG depression observed after surfactant instillation is not caused by cerebral ischemia.