The objective of this work was to determine the effect of the inflammatory response during Mannheimia haemolytica pneumonia on expression of selected antimicrobial peptides in the ruminant lung. The first study determined the presence of anionic peptide (AP) in the bronchoalveolar lavage fluid (BALF) of neonatal calves during acute inflammation. Anionic peptide was present at a similar concentration in all infected and uninfected calves and was three times higher in neonates than in adult cattle; however, BALF from neonates had little or no anti-M. haemolytica activity in vitro, compared with adult cattle. As neutrophils have an important role in pulmonary tissue damage associated with M. haemolytica infection, the effect of a selectin inhibitor, TBC1269, used on a group of infected calves, was determined. TBC1269 decreased the amount of pulmonary tissue injury in infected calves; however, it had no effect on BALF AP concentration or antimicrobial activity. The second study used the same calves to examine the presence in the lung during acute inflammation of an inducible beta-defensin, tracheal antimicrobial peptide (TAP). In addition, two molecules vital to neutrophil infiltration, interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1 were examined. Messenger ribonucleic acid (mRNA) expression of TAP and ICAM-1 was found to be rapidly upregulated; however, there was variation between individual animals that could result in suboptimal innate immunity at birth. In addition, it was found that TBC 1269 did not significantly alter TAP expression. Also, within individuals, there was positive correlation between mRNA expression of TAP and IL-8, suggesting common pro inflammatory stimuli for upregulation. In the final study, a suspected inducible ovine beta defensin, sheep beta-defensin-1 (SBD-1), was examined during acute, subacute and chronic inflammation. Surprisingly, it was found that there was no difference in SBD-1 mRNA expression in infected and uninfected sheep, nor did this expression change over time after infection. These results suggest that SBD-1 expression is constitutive in lung and is not altered during acute, subacute or chronic inflammation. The above studies demonstrate that antimicrobial peptide expression is a dynamic process in the ruminant lung during M. haemolytica pneumonia and can be markedly affected by the degree of pulmonary inflammation.