The gene expression profile of peripheral blood leukocytes (PBL) from extreme performing pigs after infection with Actinobacillus pleuropneumoniae was analysed using a custom complementary DNA (cDNA) microarray and quantitative reverse transcription-PCR (qRT-PCR). Four high performing animals with low disease-score (HP), three low performing animals with high disease-score (LP) and one medium performing animal with medium disease-score (MP) were selected for microarray profiling. PBL RNA from these eight pigs collected before and at 24h after APP infection, was examined. The study identified 92 genes that were up-regulated and four genes that were down-regulated in PBL RNA from HP pigs compared to LP pigs. The majority of differentially expressed (DE) genes were identified by virtue of their elevated expression in the HP animals at 24h post-infection. A large number of annotated DE genes are involved in innate immune response pathways. The gene expression profile of 10 DE candidate genes was further explored across the entire pig population in the same infection trial using qRT-PCR. Considerable animal-to-animal variation in PBL gene expression was observed, especially in the LP group. The qRT-PCR analysis suggested that only one true LP pig might be present in this study, which contributes significantly to the differential expression profile of the selected genes in HP animals following APP infection. This study has therefore identified a set of genes which could serve as molecular indicators for an effective immune response to APP in pigs and which could also serve as source for gene marker development in molecular genetics studies of heritable immune traits.