Human histocompatibility leukocyte antigen (HLA)-G is an MHC class Ib molecule that has been proposed to regulate immune responses during pregnancy. One of the possible mechanisms of that modulation is based on its interaction with immunoglobulin-like transcript (ILT) receptors. In this study, we show that HLA-G modifies the function of murine dendritic cells via interactions with the paired immunoglobulin-like inhibitory receptor, a homologue of the human inhibitory receptor ILT4. Triggering of the immune inhibitory receptors resulted in prolongation of allogeneic graft survival. This demonstration forms the basis for exploring and exploiting HLA-G molecules and immune inhibitory receptors in the development of a new therapeutic strategy to improve allogeneic graft survival.