The efficiency of interaction of helper T cells with memory B cells of varying histocompatibility types has been studied in an in vitro microculture system. Such studies show that I-A region matching does not necessarily determine that efficient co-operation will take place. Failure to co-operate under circumstances where T and B cells match in I-A can be attributed to radiosensitive suppressor T cells. The nature of the gene differences which provoke the activity of such suppressor cells have also been examined, and it would seem that even single S.D. differences in the MHC are sufficient to generate 'suppressor' T-cell activity.