1. Four adult patients are described whose sera showed a complete lack of gamma globulin by paper electrophoresis.
2. All four patients might have been considered "universal recipients" because of the absence of isohemagglutinins on routine laboratory tests.
3. Weak isohemagglutinins were detectable in the sera from three of the four subjects when the sensitivity of the in vitro test was increased.
4. Following intravenous administration of 4 ml. of ABO-incompatible cells, red cell survival was shortened in all of the patients, with a wide range of half-survival times from <10 minutes to as long as 9 days.
5. Although in vitro tests for antibody activity revealed no qualitative differences among the sera from the three patients with detectable isohemagglutinins, two different mechanisms of red cell removal were observed, one which entailed nearly equal activity by both liver and spleen, the other being primarily a function of the spleen.
6. The survival of incompatible cells under conditions of antibody "excess" and antibody "insufficiency" was compared in one of the patients. The findings emphasize the sensitivity of in vivo survival studies employing small volumes of incompatible cells to detect minute quantities of circulating antibody.
7. A fall in anti-A titer following the administration of group B cells to one hypogammaglobulinemic subject is interpreted as a possible in vivo example of the absorption of "cross-reacting" antibody in the ABO system.
8. In the light of the in vivo and in vitro findings, none of the 4 hypogammaglobulinemic patients in the present series could be categorized as "universal recipients."