Targeted electrical energy applied to wounds has been shown to improve wound-healing rates. However, the mechanisms are poorly understood. The aim of this study was to identify genes that are responsive to electrical stimulation (ES) in healthy subjects with undamaged skin. To achieve this objective, study authors used a small, noninvasive ES medical device to deliver a continuous, specific, set sequence of electrical energy impulses over a 48-hour period to the skin of healthy volunteers and compared resultant gene expression by microarray analysis. Application of this specific ES resulted in differential expression of 105 genes, the majority of which were down-regulated. Postmicroarray analyses revealed there was commonality with a small number of genes that have previously been shown to be up-regulated in skin wounds, including venous leg ulcers. The specific sequence of ES applied continuously for 48 hours to the skin of healthy patients has the effect of modifying expression in a number of identified genes. The identification of the differential expression in this subset of genes in healthy subjects provides new potential lines of scientific inquiry for identifying similar responses in subjects with slow or poorly healing wounds.