Understanding how vertebrates respond to hypoxia can have important clinical implications. Fish have evolved the ability to survive long exposure to low oxygen levels. However, little is known about the specific changes in gene expression that result from hypoxia. In this study we used a zebrafish cDNA microarray to examine the expression of >4,500 genes in zebrafish embryos exposed to 24 h of hypoxia during development. We tested the hypotheses that hypoxia changes gene expression profile of the zebrafish embryos and that these changes can be reverted by reexposure to a normoxic (20.8% O(2)) environment. Our data were consistent with both of these hypotheses: indicating that zebrafish embryos undergo adaptive changes in gene expression in response to hypoxia. Our study provides a striking genetic portrait of the zebrafish embryos' adaptive responses to hypoxic stress and demonstrates the utility of the microarray technology as a tool for analyzing complex developmental processes in the zebrafish.