The effect of the consumption of hypoallergenic wheat flour (HWF) on the expression of a wide spectrum of genes was analyzed by using a DNA microarray. Gene expression profiles in the liver and intestines of rats fed on a diet composed mainly of HWF were compared with those of rats fed on a normal flour-based diet. Among the eight thousand transcripts represented on the GeneChip microarray, no more than 30 genes exhibited up- or down-regulation of two-fold or more after one week or two months of HWF consumption. No adverse effects were apparent. Up-regulation of some of the genes known to respond to the interferon-gamma signal was apparent in the one-week experiment, which may be related to possible oral immunotolerance resulting from HWF feeding. This DNA microarray technology presents an efficient method for evaluating the safety of foods.