Two patients are described in whom clinically significant red blood cell alloantibodies could be demonstrated only by in vivo 51chromium (51Cr) survival studies. The first patient had experienced a severe delayed hemolytic transfusion reaction to four units of crossmatch compatible blood. Serial phenotype studies suggested the presence of a serologically undetectable anti-c (hr') antibody. 51Cr survival of c-positive red blood cells was one per cent at 24 hours, while survival of c-negative red blood cells was 80 per cent at 24 hours. The second patient had multiple red blood cell alloantibodies. An anti-c antibody was suspected but could not be convincingly demonstrated by in vitro techniques. 51Cr survival of c-positive red blood cells, however, was 57 per cent at 24 hours and 17 per cent at 48 hours. 51Chromium red blood cell survival studies should be considered whenever an unexplained hemolytic transfusion reaction occurs, or when an expected red blood cell alloantibody cannot be demonstrated by in vitro laboratory studies.