Fishes live in an aquatic environment with low or temporally changing O(2) availability. Variations in O(2) levels require many anatomical, behavioral, physiological, and biochemical adaptations that ensure the uptake of an adequate amount of O(2). Some fish species are comparatively well adapted to tolerate low O(2) partial pressure (hypoxia). The Japanese ricefish medaka (Oryzias latipes) is an important model organism for biomedical research that shows remarkable tolerance towards hypoxia. We have investigated the regulation and role of globins under hypoxia. We applied four different regimes of chronic hypoxia (24 and 48 h at PO(2) = 2 or 4 kPa) as well as acute hypoxia (2 h at PO(2) = 0.5 kPa) to adult male medaka. Changes of mRNA levels of seven globin genes (adult hemoglobin α and β, myoglobin, neuroglobin, cytoglobin 1 and 2, globin X), three hypoxia-response genes (lactate dehydrogenase b, phosphoglycerate kinase, adrenomedullin 1) and two putative reference genes (cyclophilin, acidic ribosomal phosphoprotein P0) were monitored by means of quantitative real-time reverse-transcription PCR. We observed strong upregulation of myoglobin, which is also expressed in the medaka brain, as previously demonstrated for carp, goldfish and zebrafish. The hemoglobin chains were found upregulated, whereas earlier studies found down-regulation of hemoglobin in hypoxic zebrafish. By contrast, neuroglobin mRNA was not affected by hypoxia in medaka, but had been found upregulated in zebrafish. Globin X is induced in medaka brain, but down-regulated in zebrafish. Thus, the patterns of hypoxia response of globins are strikingly different in various fish species, which can be interpreted as indication for different roles of the various globins in hypoxia response and for alternative metabolic strategies of fish species in coping with O(2) deprivation.