The distribution of the O2 carrying proteins suggests that the original transport system was a hemoglobin similar to the alpha-chain of hemoglobin A and packaged in a nucleated red blood cell. These molecules, which occur in large open fluid compartments, function as O2 stores for regular periods of hypoxia as well as carriers between sites of gas exchange. When the closed circulatory system first arose, the red blood cell was abandoned in favor of extracellular heme proteins, and the O2 storage function became less important. Alternative O2 carriers, hemerythrins, appear in the blood at about the same phylogenetic level as the intracellular hemoglobins, and their respiratory functions appear to be similar. The presence of hemoglobins instead of hemerythrins in the vertebrates may be an evolutionary accident. Still other O2 carriers, hemocyanins, arose separately in two specialized groups that left no descendants. Their O2 binding has all the adaptive features of vertebrate hemoglobin O2 binding, with unique features also. The respiratory function of the hemocyanins is largely limited to O2 transport, which makes a far greater contribution to aerobic metabolism than the O2 carriers found in simpler systems.