In vitro studies with cell lines, mainly derived from colon, have contributed significantly toward understanding the pathogenesis of rotavirus on a molecular level. However, the intestinal mucosa consists of a diversity of specialized cell types in different states of differentiation. Presumably, all these different types of cells respond differently to environmental changes, and accordingly to changes in their neighboring cells. Therefore, the regulation of genes responsible for these complex phenotypic responses in vivo may not be detected by challenging single types of cultured cells with rotavirus. To address this issue, we studied the early transcriptional response in jejunal mucosa of 3-week-old, just-weaned piglets after oral infection with virulent group A rotavirus. To assign measured responses exclusively to rotavirus, we performed these experiments in germ-free piglets. Differential expression patterns of uninfected versus infected jejunum were recorded 12 and 6 h before severe diarrhea was expected, using a homemade pig intestinal cDNA microarray [34] . The biological significance of elevated or reduced expression of these genes for rotavirus pathogenesis is discussed.