The aim of this study was to define the influence of long-term hypoxia on gene expression of tyrosine hydroxylase (TH) in the rat nucleus tractus solitarius (NTS). Animals were exposed to normobaric hypoxia (10% O2 in nitrogen) for 2 weeks. At this time, the hypoxia-induced hyperventilation reached a plateau, indicating ventilatory acclimatization. In horizontal brainstem sections, hypoxia-induced changes in TH protein and TH mRNA were assessed by immunocytochemistry and in-situ hybridization, respectively. Long-term hypoxia increased TH mRNA levels seen as both an increase in the number of grains per cell and an extension of the labeled area. The highest degree of labeling was found selectively located in caudal NTS. Hypoxia also enhanced TH immunoreactivity in the caudal NTS but this labeling extended more rostrally than that of TH mRNA. The data suggest that there is an hypoxia-induced plasticity of gene expression at the gene level in the NTS, which is associated with ventilatory acclimatization. The hypoxia model described in this study may serve as a framework for future regulatory studies.