AbstractIn recent years there has been considerable interest in the use of hemoglobin solution as a volume expander. This solution would be able to both pick‐up and off‐load oxygen as well as expand the circulating value. It is extremely important to know whether or not hemoglobin itself as well as stroma is antigenic, since an affirmative answer would preclude its use as a plasma expander.To obtain this answer, the following study was carried out. A group of white rabbits were challenged over a 21‐day period with either saline solution, hemolysates containing various concentrations of stroma, or stroma‐free hemoglobin solution. We found that stroma produced marked increase in gamma to globulin concentrations, phospholipid concentrations, and clotting times. In addition, marked thrombocytopenia was also noted. In contrast we found no such changes in animals given either saline solution or stroma‐free hemoglobin solution. The data indicate that the stroma is antigenic but that hemoglobin solution without stro