The early inflammatory response to ISCOM-Matrix was evaluated in pigs.  No side effects, determined as body temperature, appetite, activity level, reaction at the site of injection, were recorded when three doses of the adjuvant (75, 100 or 150 μg) were injected in one week old piglets. Histological examination revealed an infiltration of leukocytes, haemorrhage and necrosis in muscle 24 hours after i.m. injection of 150 μg AbISCO^®100 in pigs aged eleven weeks. At this time, different grades of reactive lymphoid hyperplasia was recorded in the draining lymphnode that was enlarged in three of the six pigs injected with AbISCO^®100. The global transcriptional response at the site of injection and in the draining lymph node was analysed in these pigs using Affymetrix GeneChip Porcine Genome Array. As compared to pigs injected with saline, a significant enrichment of gene signatures for the cell types “myeloid cells” and “plasmacytoid dendritic cells” were recorded at the site of injection. In the draining lymph node, a majority of the most upregulated genes were interferon-regulated (IRGs). A number of genes encoding cytokines / chemokines or their receptors were upregulated at the injcetion site as well as in the draining lymph node.