The ability of retinoic acid (RA) to modulate attachment of JAR choriocarcinoma multicellular spheroids to monolayers of a human uterine epithelial cell line (RL95-2) was examined using a centrifugal force-based adhesion assay. Exposure of choriocarcinoma spheroids to RA (10(-7) to 10(-5) M) over a 3-day culture period resulted in a dose-dependent decrease of attachment. Significant decreases in attachment were detected after 30 min (75 per cent versus 25 per cent) and 1 h (92 per cent versus 26 per cent) of confrontation-culture between choriocarcinoma and uterine cells for control versus 10(-5) M RA; by 5 h 100 per cent spheroid attachment was detected in all treatment groups. RA had no effect on cell proliferation in JAR spheroids, but 10(-5) M RA treatment induced a fivefold increase in secretion of human chorionic gonadotrophin (hCG), a known marker of conversion of cytotrophoblast to syncytiotrophoblast-like cells. These findings demonstrate that RA modulates cellular attachment and differentiation in choriocarcinoma spheroids in vitro.