Monocarboxylate transporters (MCTs) have been shown to be important in regulating metabolism during hypoxia in mammals. However, the role of MCTs in hypoxic survival in lower vertebrates is currently unclear. The goal of this study was to investigate the coordinated responses of MCTs along with other metabolic genes during hypoxia. Therefore, we subjected zebrafish (Danio rerio) to 1.5mgL(-1) O(2) over 48 and 96h and measured tissue-specific transcriptional changes of MCTs (1, 2 and 4), lactate dehydrogenase A (LDHa), citrate synthase (CS), and other metabolic proteins using real-time RT-PCR. There were no changes in mRNA detected in muscle at 48 and 96h. When data from both time points were pooled in brain, a significant increase was found in MCT4 (+102%) and LDHa (+28%) mRNA suggesting a preference towards glycolysis. In gills, there were increases in LDHa at 48h (+101%) and MCT1 (+24%) mRNA from pooled data suggesting that both anaerobic and aerobic metabolisms are being utilized. The heart showed the greatest changes in transcriptional regulation compared to other tissues. At 48h, increases were found in MCT1 (+117%), MCT4 (+86%), LDHa (+197%) mRNA, and pooled data showed an increase in CS (+18%) mRNA. These results suggest that the influx and efflux of lactate are both employed as strategies in cardiac tissue during hypoxia. This study has shown that fish utilize tissue-specific transcriptional regulation of MCTs along with other metabolic genes during hypoxia.