After binding its ligand, the transmembrane Notch receptor is proteolytically cleaved whereupon the Notch intracellular domain (NICD) translocates to the nucleus. NICD promotes the expression of HES, a transcriptional repressor, and Iso et al. have now identified a HES-related basic helix-loop-helix protein (HERP) as another transcriptional repressor whose expression is directly stimulated by NICD. HERP recruited mSin3, histone deacetylase 1 (HDAC1), and another corepressor N-CoR into a gene transcription inhibitory complex, whereas HES recruited Groucho/TLE. Additionally, Iso et al. found that HES and HERP homodimerized and bound to similar DNA sequences. However, HERP and HES also heterodimerized and blocked transcription better than either homodimer. These data suggest that repressors and their related higher-order protein complexes in the Notch signaling system can interact in different combinations to provide differing levels of transcriptional repression.