The aim of this study was to quantify lung oxidant stress after short-term ozone exposure as reflected by 8-isoprostane concentrations in exhaled breath condensate (EBC) and to investigate the effects of inhaled budesonide on this response. 8-Isoprostane is a prostaglandin-F_2α isomer that is formed in vivo by free radical-catalyzed peroxidation of arachidonic acid. EBC is a noninvasive method to collect airway secretions. We undertook a double-blind, randomized, placebo-controlled, crossover study with inhaled budesonide (800 μg) or placebo twice daily for 2 weeks prior to ozone exposure (400 parts per billion) for 2 h in nine healthy nonsmokers. Exhaled 8-isoprostane was measured by an enzyme immunoassay. 8-Isoprostane was increased 4 h after ozone exposure compared to pre-exposure values in both placebo (36.9 ± 3.9 pg/ml, mean ± SEM, vs. 16.9 ± 0.7 pg/ml; p < .001) and budesonide groups (33.4 ± 2.6 pg/ml vs. 15.8 ± 0.3 pg/ml; p < .001). Pretreatment with budesonide did not affect the increases in 8-isoprostane (mean differences 3.4 pg/ml, 95% CI −8.9 to 15.7, p = .54). Short-term ozone exposure causes acute increase in lung oxidative stress as reflected by exhaled 8-isoprostane. This increase is resistant to pretreatment with a high dose of inhaled budesonide.