Low dissolved oxygen, hypoxia, is a prevalent stressor in aquatic environments arising from natural and anthropogenic events. Included in the biological responses to hypoxia are changes in gene expression that are coordinated by the hypoxia-inducible factor (HIF) family of transcription factors. The paradigm for HIF signaling is that alpha subunits (HIFα) are degraded during normoxia, but degradation is suppressed at low oxygen, leading to the accumulation of HIFα, dimerization with beta subunits, and regulation of target gene transcription. In fish, there is evidence that HIF1α mRNA levels also increase during hypoxia, but these measurements are from experiments without corresponding protein levels. Therefore, in this study, we addressed two questions. Do levels of HIFα mRNA increase after short-term hypoxic exposure? Do levels of HIFα mRNA correlate with protein levels measured in the same tissues? Fundulus grandis, a small, abundant, estuarine fish, was exposed to approximately 1 mg/l O₂ for 6 or 24 h, after which RNA was extracted from liver, gills, ovary, and skeletal muscle. HIF1α mRNA levels were determined by quantitative PCR. The results show that there were no changes in HIF1α mRNA under these conditions, even when HIF1α protein levels were significantly elevated. Our results support a role for protein stabilization, rather than new transcription in the initial response of fish to low oxygen, in agreement with the paradigm developed for HIF signaling in mammalian cells.