Trophoblast cells, dispersed by trypsin digestion of human term placental villi and purified on Percoll gradient, were maintained in serum-containing medium as monolayer cultures up to 7 days. The initially mononucleated cells, probably cytotrophoblasts, differentiated in culture within 90 h to multinucleated syncytiotrophoblast-like cells. The enigmatic binding of human immunoglobulin G (hIgG) to these cells was studied and compared to the well-known binding of hIgG to cultured human monocytes. Binding of hIgG to cultured trophoblasts at 4 degreesC reached steady state by 0.5-1 h, increased about two- to threefold after 90 h in culture and was linear throughout all concentrations tested (0.00067-132 microM). Fc fragments and even F(ab')2 fragments were found to bind to a similar extent to trophoblasts as the complete hIgG molecules. In contrast, in experiments with cultured monocytes, saturation of hIgG binding could be demonstrated. The binding of complete hIgG molecules and of Fc fragments to monocytes was similar whereas binding of F(ab')2 fragments to monocytes was significantly lower. Our results suggest that, despite morphological and at least partially functional differentiation of trophoblast cells in primary culture, no measurable amounts of functional Fc receptor for monomeric hIgG was expressed.