The pulmonary microenvironment is a primary target for alpha particles like those emitted by inhaled radon and its progeny. While exposure to alpha particles has recently been associated with the generation of extracellular and intracellular reactive oxygen species (ROS; Cancer Res. 57, 3963-3971, 1997), little is known about how exposure to alpha particles may affect the generation of oxidative stress-related mediators in the respiratory tract. Interleukin-8 (IL8) is a cytokine recognized for its potent role as a chemoattractant and activator of polymorphonuclear leukocytes. Oxidative stress can up-regulate expression of the gene that encodes IL8 (IL8) in a variety of cell types. In this study, we set out to investigate a potential linkage between the generation of ROS and production of IL8 in alpha-particle-irradiated normal human lung fibroblasts. ELISA revealed that exposure of the fibroblasts to low doses of alpha particles (3.6-19 cGy) caused significant increases in generation of the IL8 protein as early as 30 min after irradiation. Northern blot analyses revealed that such increases were associated with increased IL8 mRNA levels. Cells exposed to alpha particles in the presence of antioxidants, i.e. superoxide dismutase and dimethyl sulfoxide, resulted in significant decreases in extracellular IL8 protein levels. Similar results were obtained with cells treated with dexamethasone, an inhibitor of transcription. Our results indicate that alpha-particle-induced increases in production of IL8 occur temporally in parallel with elevated production of ROS. Conceivably, such production of IL8 induced by alpha particles may contribute to an inflammatory response in the lower respiratory tract. Additionally, the promitogenic effects of IL8 may be a factor in hyperplastic responses in the airway epithelial cells to inhaled radon and radon progeny and perhaps other stresses associated with ROS.