ABSTRACT: Here we report the genome-wide transcriptomic changes resulting from low N stress, low water (W) stress and both the stresses (N-W-) from root and shoot tissues in two rice genotypes,IR 64 (IR64) and Nagina 22 (N22).The former is a better N user but drought stress sensitive while the latter is the internationally known drought tolerant variety but with poor NUE. Though it is well known that adverse effect of the major abiotic stress, drought, on rice is exacerbated by low supply of N, there are no studies yet on the genome-wide effect of co-occurrence of these two major inputs, water and N. We identified a total of 8926 unique differentially expressed genes (DEGs) across all stress treatments compared to optimal input supply. Interestingly, we identified only 1174, 698 and 903 DEGs in root tissues of IR 64, and 1197, 187 and 781 DEGs in N22; while nearly double the number of DEGs were found in shoot tissues, i.e., 3357, 1006 and 4005 in IR 64 and 4004, 990 and 2143 DEGs (log 2 fold change and FDR p value <0.05) in N22 under N-W+, N+W- and N-W-stress treatments.Overall, more than 70% of the genes showed a similar response in both the genotypes. Of the 15 differentially expressed N transporter genes including the high affinity nitrate transporters, ammonium transporters and urea transporter, IR64 showed differential expression in all of them whereas N22 showed differential expression only in 11 under N-W-and/or N-W- stress(es). Four of the N transporters (NRT2.1, NRT2.4, OsNAR2.2 and OsAMT2_1) were also differentially expressed under N+W-condition. A low affinity nitrate transporter, OsNPF7.2, was differentially expressed only in N22 shoots under all three stress conditions implicating its genotype specific role in nitrate transport in above ground part. Genes involved in allantoin and melatonin metabolism were down regulated only under N stress in both the genotypes but not under drought. Three negative regulators of N stress, NIGT1, OsBT and OsACTPK1 were downregulated in IR64 while NIGT1 transcript alone was downregulated in N22 under N stress. Of the 8926 DEGs, 26.15% were completely novel represented by 916 conserved hypothetical proteins and 1418 hypothetical conserved_gene/gene/proteins.