The virus-immune responder characteristics of thymocytes, spleen and lymph node (LN) cells from (P1 X P2)F1 leads to P1 radiation chimeras have been examined sequentially at weekly intervals. Adoptively-transferred thymocytes generate strong cytotoxic thymus-derived lymphocyte (CTL) responses from 28 to 100 days after reconstitution with bone marrow, which are almost invariably restricted to recognition of virus presented in the context of P1. This pattern of H-2 restriction is also maintained for spleen and LN cells from the [(H-2kXd)F1 leads to H-2k] and [(H-2kXb)F1 leads to H-2k] combinations but there is random emergence of reactivity to H-2k+virus for peripheral lymphoid cells from [(H-2KkXb)F1 leads to H-2b] chimeras. Treatment of established [(P1 X P2)F1 leads to P1] chimeras with a low dose of cyclophosphamide (Cy) did not lead to the emergence of significant CTL effector function for P2 + virus. Also, administration of a large dose of Cy prior to irradiation of the chimera recipients did not modify the H-2 restriction profile of the chimera, though the level of CTL responsiveness associated with the appropriate H-2 type was apparently enhanced.