Any serious efforts at prolonged mechanical support of the circulation must consider the biologic tolerance to continuing damage imposed by the support system. Such damage includes the immediate breakdown of red blood cells, measured as hemolysis, the presence of the envelopes or “ghosts” of the cells in the circulation, and other, more subtle, forms of damage to the blood cells which may impair their ability to survive or function over a normal life span. The experiments reported herein were performed in an effort to define the limit of the unanesthetized intact animal to accept and deal with free hemoglobin, red blood cell ghosts, and chronic blood loss or destruction over a prolonged period of time. In addition, preliminary experiments have been undertaken to identify the nature of a diffuse sublethal defect imposed upon red blood cells by pumping. Each of these experiments will be detailed separately.