We have previously shown that Oryza sativa L. Pokkali maintains higher levels of transcripts under non-saline conditions, which are otherwise induced under salinity in the sensitive genotype-IR64. We wanted to test this hypothesis of differential gene regulation further, within the members of a given stress responsive gene family, which share significant structural and functional similarities. For this purpose, we chose to work on the two-component system (TCS family) which plays an important role in stress perception and signal transduction under hormonal, abiotic stress, light and developmental regulation. We present data to show that all members of TCS family, including sensory histidine kinases, phosphotransfer proteins and response regulators, are having differential transcript abundance (under both non-stress and salinity stress conditions) in contrasting rice genotypes. Further, under non-stress conditions, transcript abundance for all TCS members (except RR21) was found to be higher in the salt-tolerant genotype-Pokkali. TCS transcripts are otherwise induced by salinity stress to a relatively higher level in the sensitive cultivar IR64. A few of these members were also found to be localised within important salinity-related quantitative trait loci identified earlier. Based on the above findings, we propose that the TCS members may have a significant role in salinity tolerance in rice and can serve as useful 'candidate genes' for raising salinity-tolerant crop plants.