Leukotoxin (LKT) is a virulence factor for Mannheimia haemolytica. In this study, bovine alveolar macrophages (BAMs) were challenged with wild type (wt) and LKT deficient (lkt(-)) M. haemolytica at a concentration of 1 bacterium/BAM and the cytokine response was quantified by ELISA and real-time reverse transcriptase-PCR. Significant increases in protein concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were observed in supernatants obtained from BAMs challenged with the lkt(-) strain of M. haemolytica compared with wt challenged BAMs. There were no significant differences in mRNA expression of TNF alpha IL-1 beta, IL-6, IL-8 or IL-10 between BAMs challenged with the lkt(-) strain of M. haemolytica compared with wt challenged BAMs. BAMs challenged with the wt strain exhibited, on average, 43% more cytotoxicity than lkt(-) challenged BAMs (P <0.01). Published by Elsevier Ltd.