Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants who are mechanically ventilated due to respiratory distress. The disease consists of an initial inflammatory influx of neutrophils to the lungs, followed by long-term chronic fibrosis of the lung tissue. The antigenic repertoire that initiates the inflammatory component of BPD has not been defined. Furthermore, the repertoire of cytokines responsible for attracting neutrophils to the lung and the mediators of pathogenesis in BPD have not been characterized. Mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum have been isolated from the lungs of infants that developed BPD and yet have not been widely recognized as potential initiators of the inflammatory component of BPD. In the studies described here, we examined the ability of both viable and heat-killed Mycoplasma hominis to elicit type II epithelial cell production of cytokines that are chemotactic for polymorphonuclear leukocytes (PMNs), particularly interleukin-8 (IL-8) and epithelial cell-derived neutrophil-activating peptide (ENA-78). The results of these studies demonstrate that M. hominis and M. hominis antigen are potent stimulators of type II epithelial cell-derived IL-8 and ENA-78. Thus, these data strongly suggest that the presence of M. hominis in the lungs of premature infants may initiate the inflammatory component of BPD by inducing epithelial cell production of cytokines chemotactic for PMNs. Furthermore, these data suggest that the onset of the inflammatory component of BPD likely precedes, and is independent of, the recruitment and activation of alveolar macrophages.