A wide range of organismic, physiological and biochemical adjustments to improve oxygen transfer is observed in fish exposed to environmental hypoxia and during anemia. Many fish species of the Amazon obtain oxygen directly from air when water oxygen is low. The accessory air-breathing organs include modifications of the gills, mouth, stomach and intestine, and swimbladder vascularization. Other species extend the lower lip and skim to improve oxygen uptake from the oxygen-rich surface layer of the water. The amount of oxygen uptake from air was estimated for Hoplosternum littorale and Lipossarcus pardalis. In addition, the oxygen uptake from the water surface was estimated for Colossoma macropomum. Blood oxygen content was reduced by 30% in Hoplosternum littorale and Colossoma macropomum and 70% in Lipossarcus pardalis if they were denied access to air. Adjustments of intraerythrocytic levels of ATP and GTP significantly improve oxygen transfer in fish during environmental hypoxia and anemia. In contrast to environmental hypoxia, intraerythrocytic levels of ATP and GTP increase during anemia in fish facilitating oxygen unloading to the tissues. It is suggested that the increase in ATP and GTP levels during anemia occurs because the conditions required to increase the activity of adenylate and guanylate phosphate synthetic pathways are similar.