To find out whether immunoglobulins are able to recognize foreign antigens in the context of syngeneic MHC determinants, an effort was made to trigger the production of MHC-restricted antibodies by syngeneic Sendai virus (SV)-infected cells using the spleen-fragment culture technique. Antibodies were found that mimicked MHC-restricted antibodies by recognizing MHC+SV better than MHC alone. However, the binding was not specific for SV and also occurred on mitogen-stimulated (SV-) or influenza virus-infected cells. We describe the production of H-2 class I-specific lymphocytotoxic antibodies by primary B cells responding to syngeneic SV-infected cells. No viral-specific, H-2-restricted antibodies were found.