The global changes in gene expression in injured murine skin were characterized following a second-degree scald burn. Dorsal skin was harvested from uninjured and from burned mice at 2 h and at 3 and 14 days following immersion in 65 degrees C water for 45 s. Gene expression was surveyed using an Affymetrix U74Av2 GeneChip, and patterns of gene expression were analyzed using hierarchical clustering and supervised analysis. Burn injury produced significant alterations in the expression of a number of genes, with the greatest changes seen 3 and 14 days after the scald burn. Using a supervised analysis with a false discovery rate of 1% or 5%, differences in the expression of 192 or 1,116 genes, respectively, discriminated among the unburned skin and the three time points after the burn injury. Gene expression was primarily a transient and time-dependent upregulation. The expression of only 24 of the 192 discriminating genes was downregulated after the burn injury. No gene exhibited a sustained increase in expression over the entire 14 days following the burn injury. Gene ontologies revealed an integrated upregulation of inflammatory and protease genes at acute time intervals, and a diminution of cytoskeletal and muscle contractile genes at 3 or 14 days after the injury. Following a second-degree scald burn, global patterns of gene expression in the burn wound change dramatically over several weeks in a time-dependent manner, and these changes can be categorized based on the biological relevance of the genes.