Background. cis and/or trans regulatory divergence within or between related taxa on a genome-wide scale has been largely unexamined in crops, more so, the effect of stress on cis/trans architecture. In this study, the indica genotypes IR64, an elite drought-susceptible lowland variety, and Apo (IR55423-01 or NSIC RC9), a moderate drought-tolerant upland genotype together with their hybrid (IR64 × Apo) were exposed to non-and water-stress conditions. Evidence of cis and/or trans regulatory differences was tested between these two indica rice genotypes.Results. By sequencing (RNA-seq) the parents and their hybrid, we are able to map genes diverging in cis and/or trans factors between the two genotypes. Under non-stress conditions, cis dominantly explains (11.2%) regulatory differences, followed by trans (8.9%). Further analysis showed that water-limiting conditions largely affect trans and cis + trans factors.Between the two inbred lines, Apo appears to exhibit higher expression fold change of genes enriched in "response to stress" and "photosynthesis" under non-and water-stress conditions.On the molecular level, cis and/or trans regulatory divergence explains their genotypic differences and differential drought response.Conclusions. Parent-hybrid RNA-seq has the potential to identify genes diverging in cis and/or trans factors even between intra-sub-specifically related genotypes. By comparing cis/trans landscape under stressed and unstressed conditions, this approach has the ability to assess the impact of drought on gene expression. Computational analysis and association of several drought-yield QTL markers with cis-and/or trans-diverging genes provide converging evidences suggestive of a potential approach to identify trait-associated candidate genes using hybrids and their parents alone.3