Nitrogen is an essential mineral nutrient and is required in great abundance for plant growth and development. Insufficient nitrogen triggers extensive physiological and biochemical changes in plants which constitute a set of adaptive responses to nitrogen limitation. In this study, to determine the genome-wide transcriptome response to nitrogen limitation, Arabidopsis plants were grown with limiting (3 mM) and sufficient (10 mM) nitrate, respectively, and their gene expression profiles were analyzed using Affymetrix GeneChip arrays. In addition to inducing the adaptive responses in Arabidopsis, nitrogen limitation altered the expression levels of 629 genes with 340 up-regulated and 289 down-regulated. The up-regulated group included the genes involved in protein degradation and the biosynthesis of anthocyanin and phenylpropanoids. The down-regulated group contained the genes functioning in photosynthesis and in the synthesis of nitrogenous macromolecules such as chlorophyll, proteins, amino acids and nucleotides. Numerous nitrogen limitation responsive genes encode transcription factors, signal transduction components, and proteins required for hormone synthesis and response. The Arabidopsis nitrogen limitation adaptation mutant (nla) is defective in developing the nitrogen limitation adaptive responses. The microarray analysis revealed that the absence of the functional NLA in the nla mutant extensively altered its responsive transcriptome to nitrogen limitation. In this mutant 1122 genes were up-regulated and 622 repressed. It was also found that the nla mutant phenotype was associated with the early induction of senescence-associated genes. This study presents a genome-wide view of Arabidopsis transcriptome response to nitrogen limitation and its regulation by NLA, and provides information to probe the molecular mechanism controlling plant adaptability to nitrogen limitation.