Salmonella is a pathogen normally found in the gastrointestinal tract of poultry. The objective of this study was to determine changes in avian beta-defensin (AvBD) and liver-enriched antimicrobial peptide 2 (LEAP2) mRNA following Salmonella challenge. Day of hatch chicks were challenged with 10(6), 10(7) or 10(8) colony-forming units (cfu) of Salmonella typhimurium. There were dose-, tissue- and age-specific changes in AvBD and LEAP2 mRNA. At 1-day post-infection (dpi) there was a transient upregulation of AvBD1, 8, 10 and 12 mRNA in the 10(8) cfu group. At 5 dpi, all seven AvBD mRNA were downregulated in the ileum, while only AvBD1, 6, 10 and 11 mRNA were downregulated in the jejunum and AvBD6, 8, 10, 12 and 13 were downregulated in the cecum. At 7 dpi, there was downregulation of all seven AvBD mRNA in the duodenum and downregulation of selected AvBD in the jejunum, ileum and cecum. LEAP2 mRNA was downregulated at all doses of Salmonella in the cecum at 1 dpi and in the ileum at 5 dpi. In summary, Salmonella infection caused an initial upregulation followed by a downregulation of AvBD mRNA.