Enterotoxigenic Escherichia coli (ETEC) K88 is a common cause of post-weaning scours in piglets. Supplementation of the post-weaning diet with pharmacological levels of zinc oxide reduces the incidence and severity of scours (Carlson et al 2004), in particular that caused by ETEC K88 (Owusu-Asiedu et al. 2003). Piglets reared outdoors pre-weaning also perform better post-weaning than those reared indoors, with an increased growth rate (Miller et al, 2007). The objective of this study was to identify genes that are differentially expressed in the small intestine of the ETEC-challenged piglet in response to dietary ZnO supplementation and outdoor rearing, to increase understanding of the mechanism by which these factors exert their effects.