Surfactant instillation often causes transient EEG suppression, the cause remaining unknown. To compare the timing of the EEG changes with the timing of the changes in blood gases and systemic circulation we compared two administration modes: 20 preterm infants were randomly assigned to receive the initial dose of surfactant divided into two or six aliquots. Heart rate, blood pressure and transcutaneous blood gases were measured continuously, while left ventricular output was estimated intermittently. No difference in blood gas response was found between the groups, whereas the circulatory changes occurred more gradually with six aliquots. EEG suppression was similar in the two groups and not related to the circulatory or the respiratory changes. Left ventricular output increased in all patients following surfactant instillation. We conclude that the EEG suppression is not directly related to alterations in blood gases or systemic circulation.