Objective: Oxygen toxicity causes chronic bronchopulmonary dysplasia (BPD) in extremely proterm infants. Polyunsaturated fatty acids (PUFA) and plasmalogens are the two main substrates for lipid peroxidation in the pulmonary surfactant. In the present study, we tested whether low concentrations of both were associated with development of BPD and whether both were further reduced during mechanical ventilation with oxygen. Design: Prospective, noninterventional, descriptive study. Setting: Level III neonatal intensive care unit in a university hospital. Patients: In 25 extremely low birth weight infants with respiratory distress syndrome, tracheal aspirates were collected immediately after birth and in the following 4 days. As control, tracheal and pharyngeal aspirates were collected from healthy infants immediately after birth. The amount of PUFA and dimethylacetals (DMA, representing plasmalogens) was determined gaschromatographically. Interventions: None. Measurements and Main Results: The relative percentages of PUFA and DMA on all fatty acids in non-BPD infants (PUFA% 26 ± 8.9, DMA% 3.5 ± 1.2) were higher compared with infants who developed BPD (PUFA% 14.5 ± 3.8, DMA% 1.8 0.9). In term healthy infants, DMA% and PUFA% were in the same range as in the BPD group. The higher levels found for non-BPD infants decreased after day I to values equal to the BPD group and remained low. Conclusions: The results suggest that initially higher levels of PUFA and plasmalogens in the tracheal effluent are associated with a reduced risk of developing BPD and are reduced during the first day of ventilation.