To examine whether prematurity significantly changes the lung inflammatory response to oxygen, rabbit lung explant cultures were exposed to 95% or 5% oxygen for 24 hours. Interleukin (IL)-8 protein concentrations from homogenates of the premature lung rose significantly after hyperoxia (6.8 +/- 1.8 in 5% O2 to 45.7 +/- 21.3 pg/microg protein in 95% O2) but not in the term lung (15.9 +/- 6.7 to 20.4 +/- 4.3 pg/microg protein). There was no change in IL-8 mRNA after hyperoxia in either age group. Preterm lungs demonstrated higher IL-8 levels by fluorescence-activated cell sorting (FACs) analysis and immunohistochemistry. This model may help determine why premature lungs are more susceptible to oxygen-induced disease.