Resting CD8+ and CD4+ murine T cells become efficiently activated by the superantigen (SA) staphylococcal enterotoxin B (SEB). Limiting dilution experiments reveal that roughly every third CD8+ or CD4+ T cell could be induced to proliferate. Surprisingly, besides CD8+ T cells, also CD4+ cells acquire a high cytolytic activity upon activation with SEB. Both subpopulations only lyse MHC class II positive target cells in the presence of SEB. However the recognition of SEB by CTL is independent of the haplotype of the MHC, i.e. is MHC-unrestricted. In addition the recognition of SEB is independent of the coreceptor molecules CD4 and CD8, respectively.