An analysis of the pattern of expression of the mouse placental hormone prolactin-like protein A (PLP-A) has revealed that this hormone is expressed exclusively in secondary trophoblast giant cells but not in primary giant cells. Thus, PLP-A serves as a marker for a subset of giant cells. Recent results have indicated that PLP-A binds to and inhibits the activity of natural killer cells, and thus, the localized expression of PLP-A may be important for regulating the activity of this class of T lymphocytes in a restricted region of the implantation site. Previous studies indicated that the transcription factor GATA-2 is required for the trophoblast giant cell-specific expression of two other hormones in the prolactin family, placental lactogen I and proliferin. In the absence of GATA-2, PLP-A continues to be expressed, but in this mutant background, PLP-A mRNA is detected in both primary and secondary giant cells. Thus, GATA-2 contributes both to positive and negative regulation of trophoblast giant cell-specific gene expression, and this factor apparently plays an important role in generating or maintaining the distinct functions of secondary, compared with primary, trophoblast giant cells.