Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has also been implicated in placental growth and development. In this study we have performed a detailed immunohistological localization of the low affinity GM-CSF receptor (GM-CSF-R alpha) in human first trimester implantation site and non-pregnant endometrium. We have also investigated receptor expression and GM-CSF binding in vitro by normal first trimester trophoblast using flow cytometric analysis and compared this with JEG-3 and JAR choriocarcinoma cells. In the first trimester, the GM-CSF-R was found to be present on villous cytotrophoblast and all populations of extravillous trophoblast. Expression by villous syncytiotrophoblast was weak or absent, but this increased markedly by term. GM-CSF-R were also expressed by fetal Hofbauer cells within the mesenchyme of the chorionic villi and by uterine glandular epithelium and decidual macrophages within maternal decidua. GM-CSF-R was not expressed by glands in proliferative phase endometrium but began to appear during the secretory phase, suggesting hormonal regulation of the receptor on uterine glandular epithelium. Flow cytometric comparison of normal isolated first trimester trophoblast and JEG-3 and JAR choriocarcinoma cells revealed two- to threefold higher surface expression of GM-CSF-R by choriocarcinoma cells and higher binding capacity for rhGM-CSF than normal trophoblast. These results suggest that GM-CSF may regulate growth and development of human trophoblast. GM-CSF may also influence placental development and function by acting via decidual and fetal macrophages, and uterine glandular epithelium, which are the other cell populations to express the receptor.