Lymphoid cells from C57BL/6 mice homozygous for the me gene exhibit multiple phenotypic and functional abnormalities from early as one week of age. In the B cell population these include a reduction in the frequency of detectable surface Ig+ cells, alterations in the level of expression of surface IgM and IgD, an increase in the frequency of large cells, plasma cells and TNP-specific plaque forming cePS. Together these findings provide strong evidence for polyclonal activation of B cells. The high level of expression of xenotropic MuLV gp70 by me/me spleen and lymph node cells provides further evidence for lymphoid cell activation. In preliminary studies, me/me T cells appeared to be phenotypically and functionally less affected by the me gene. The distribution of Thy 1.2 on the surface of spleen and lymph node T cells varied from low to normal and the mitogenic responses to Con A and PHA were depressed. It remains to be determined what the basic deficiency in me/me mice is and whether it affects primarily B cells or all lymphoid cells.