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Aim of the study: To analyze the course of leaf water status, water-use efficiency and growth in Eucalyptus grandis and hybrids throughout seasons with different rainfall. Area of study: The study was conducted in northern Uruguay. Methods: A randomized block trial was established containing E. grandis (ABH17), E. grandis × Eucalyptus camaldulensis (GC172), E. grandis × Eucalyptus tereticornis (GT529), and E. grandis × Eucalyptus urophylla (GU08). Predawn leaf water potential (Ψpd) and midday leaf water potential (Ψmd) were measured every six weeks from the age of 16 months, throughout two growing seasons. Stomatal conductance (gs), net photosynthetic rate (A), and leaf-level transpiration (E) were measured once in each growing season, along with leaf carbon isotope discrimination (∆13C) and tree growth. Stomatal density and distribution were studied. Results: ABH17 and GU08 had the lowest daily fluctuation of leaf water potential and showed stronger stomatal regulation; they were hypostomatic, and stomata on the adaxial leaf surfaces remained immature. GC172 and GT529 (Red-Gum hybrids) were amphistomatic and transpired more intensively; they were less efficient in instantaneous and intrinsic water use and grew faster under high soil moisture (inferred from rainfall). Under such conditions, GC172 reached the highest gas-exchange rate due to an increase in tree hydraulic conductance. ABH17 and GU08 were hypostomatic and used water more efficiently because of stronger stomatal regulation. Research highlights: Red-Gum hybrids evidenced less water use efficiency due to lower stomatal regulation, different stomatal features, and distinct growth patterns as a function of soil moisture (inferred from rainfall). Keywords: Eucalypt hybrids; stomatal conductance; water-use efficiency; transpiration. Abbreviations used: Ψpd:predawn leaf water potential;Ψmd: midday leaf water potential; ΔΨ: daily fluctuation of leaf water potential ( ; A: net photosynthetic rate, E: leaf transpiration rate, gs: stomatal conductance, WUE: instantaneous water-use efficiency; WUEi: integrated water-use efficiency; A/E: leaf photosynthesis-to-leaf transpiration ratio; ∆13C: leaf carbon isotope discrimination; K: tree hydraulic conductance; E/∆Ψ: ratio between leaf transpiration and daily fluctuation of leaf water potential; δ13C: natural abundance of 13C.