To gain a comprehensive understanding of the molecular mechanisms underlying the effects of dietary protein on alternations in physiologic and pathologic status, the GeneChip microarray system was used to investigate the consequences of two different states of protein malnutrition on gene expression in rat liver. Expressions of 281 genes were increased or decreased by twofold or more by treatment with a protein-free diet for 1 wk compared with control rats fed a casein diet. Similarly, 111 genes were affected in rats fed a wheat gluten diet compared with those fed the casein diet. Although some of the genes identified were known to respond to protein nutrition, a majority were newly identified as responders to protein nutritional status. Interesting findings included the drastic changes in the levels of genes for Id (inhibitor of DNA binding) proteins, which are involved in the regulation of multiple genes, and of a set of genes in the pathway of cholesterol biosynthesis and disposal. This study represents a step toward a more global understanding of gene expression changes in states of protein malnutrition.