AbstractThe lymph node cells (LNC) activatedin vivoby liver regeneration following partial hepatectomy of mice (primed lymph node cells) respond to regenerating liver cellsin vitrowith typical secondary immune response characteristics (Miyahara, S. et al.,Eur. J. Immunol.1983.13: 878). These LNC activatedin vivosuppress the proliferation of responder lymphocytes cultured with mitomycin C‐treated regenerating syngeneic liver cells (sMLHLR). The suppressive activity was already present in LNC 4 days after partial hepatectomy and remained unchanged for at least 16 days. These primed LNC were effective not only on sMLHLR but also on syngeneic mixed lymphocyte culture (sMLR) and allogeneic mixed lymphocyte culture, of which responder cells share the I‐A (I‐B) subregions of the major histocompatibility complex (MHC) with primed LNC. At least one cell in the suppressor circuit is a T cell. The primed LNC restimulatesin vitrowith regenerating liver cells (in vitroreactivated primed LNC) suppressed the proliferation of syngeneic responder cells in sMLR, but not of cells from congeneic mice differing from thein vitroreactivated primed LNC at a cluster of genes linked to the Ig locus. Thus the suppressive activity of primed LNC is controlled by the I‐A (I‐B) subregions of the MHC and that ofin vitroreactivated primed LNC by genes in the Ig region. The role of these suppressive cells in liver regeneration is