Information was sought on whether B cells undergo abnormal differentiation in F1 leads to parent chimeras (irradiated parental-strain mice reconstituted with F1-hybrid bone marrow cells). As assessed by collaborative responses to sheep erythrocytes in vivo, three different types of T cells restricted to interaction with strain a H-2 determinants were shown to collaborate as effectively with heterologous F1 leads to b chimera B cells as with homologous F1 leads to a chimera B cells. This applied to both primed and unprimed B cells, to IgM- and IgG-antibody formation and to production of Ig allotype. Thus, unlike T cells, B cells from F1 leads to parent chimeras behaved indistinguishably from normal F1 B cells. F1 leads to parent chimeras were also examined for their capacity to present antigen to normal F1 T cells in vivo. The results suggested that the antigen-presenting cells in these chimeras were no different than in normal F1 mice. Collectively these data imply that, at least in the situation studied, raising F1 stem cells in a parental-strain environment has a marked effect on T-cell specificity but does not discernably influence the differentiation of B cells or macrophage-like cells.