show Abstracthide AbstractChanges in nutrient dose have dramatic effects on gene expression and development. However, an outstanding question is whether organisms respond to changes in absolute nutrient amount (moles) vs. concentration relative to water (molarity). This basic knowledge gap can be tackled in plants, as soil drying (e.g. drought) can alter nutrient concentration, without changing its absolute amount, and results have practical implications for agriculture. To investigate, we exposed rice to a factorial matrix varying nitrogen (N) dose and water (W) combinations, and quantified transcriptome and phenotype responses. Using linear models, we identified distinct dose responses to either N-moles, W-volume, N-molarity (N/W), or a synergistic interaction (NxW). Importantly, genes whose expression patterns are best explained by N-dose and W interactions (N/W or NxW) in seedlings were associated with crop outcomes in replicated field trials. Such N-by-W response genes may assist future efforts to develop crops resilient to increasingly arid, low nutrient soils.