The balance of inhibitory and activating natural killer (NK) receptors on maternal decidual NK cells, most of which are CD56(bright), is thought to be crucial for the proper growth of trophoblasts in placenta. A lectin-like NK receptor, CD94/NKG2, is the receptor for human leukocyte antigen (HLA)-E, which is expressed on trophoblasts. To clarify the mechanism regulating the activity of decidual NK cells during pregnancy, we investigated the expression patterns of inhibitory NK receptor, CD94/NKG2A, and activating receptor, CD94/NKG2C, on decidual NK cells in an early stage of normal pregnancy and compared them with those on peripheral NK cells, most of which are CD56(dim). The rate of NKG2A-positive cells was significantly higher for decidual CD56(bright) NK cells than for peripheral CD56(dim) NK cells, but the rates of NKG2C-positive cells were comparable between the two cell types. Interestingly, peripheral CD56(dim) NK cells reciprocally expressed inhibitory NKG2A and activating NKG2C, but decidual CD56 (bright) NK cells that expressed activating NKG2C simultaneously expressed inhibitory NKG2A. The co-expression of inhibitory and activating NKG2 receptors fine-tune the immunoregulatory functions of the decidual NK cells to control the trophoblast invasion in constructing placenta. (c) 2006 Elsevier Ireland Ltd. All rights reserved.