Preconditioning to lowered oxygen levels (hypoxia) may occur when an animal is subjected to non-lethal levels of hypoxia and then returned to normoxic conditions. During a subsequent exposure to hypoxia, the pre-exposed animals may exhibit increased tolerance compared to naive animals. I have demonstrated, by analysis of critical PO2's (Pcrit), that zebrafish embryos can be preconditioned to hypoxia. Preconditioned embryos display a lower Pcrit than controls, indicating a heightened ability to endure hypoxic conditions. The role of the hypoxia inducible factor-1 (HIF-1) in promoting hypoxic preconditioning was examined. To determine the role of HIF-1 in preconditioning, embryos deficient in HIF-1alpha (using antisense oligonucleotide morpholinos) were assessed under hypoxic conditions. No significant difference between preconditioning capacities of control- and HIF-1alpha deficient embryos was observed. In addition to assessing Pcrit, a suite of hypoxia responsive genes were analysed by real time PCR. IGFBP-2 showed a significant decrease in expression in the HIF-1alpha deficient embryos, and EPO showed a significant increase in HIF-1alpha deficient embryos. All other genes examined showed no significant change between treated and control embryos.