Haemophilus parasuis is the aetiological agent of Glässer's disease, which has received more attention in the past decade due to the increasing economic losses in the pig industry worldwide. Little is known about the mechanisms by which H. parasuis survives in the host. In this study, selective capture of transcribed sequences (SCOTS) was used to identify H. parasuis genes upregulated in necrotic porcine lung 7 days post infection. Thirty-eight genes were identified that were upregulated during infection of the lung tissue of pigs, compared with growth in culture medium. In two examples chosen gene expression was not confined to the lungs, there being variation between tissues. The data support biofilm formation being an important mode of growth for colonization and/or persistence. Results from the in vitro studies suggest that, as for other pathogens, iron and oxygen restriction and heat stress are important environmental signals to regulate gene expression. This study has identified genes of H. parasuis that are upregulated during infection of porcine lung tissue as compared with in vitro growth conditions.