Hemopexin binds proto-, meso-, or deutero-ferriheme with high affinity, forming an equimolar, low-spin complex. The ferroheme-hemopexin complex, which coordinates with CO and readily autoxidizes, is also low-spin. Formation of the ferriheme-hemopexin complex requires essential histidine and tryptophan residues and induces changes in the protein's tertiary structure. These changes may be important for the uptake of the heme-hemopexin complex by hepatocytes. Hemopexin also binds other porphyrins including protoporphyrin IX, and uro- and coproporphyrins I and III in a 1:1 molar ratio, but they are readily displaced by heme and do not produce discernable changes in the protein's conformation. In preliminary experiments, a selective interaction in vitro between heme-hemopexin and isolated rat hepatocytes has been demonstrated. This information is used as the basis for proposed models of the heme-binding site of hemopexin and of the interaction of heme-hemopexin with the parenchymal cells of the liver.