The synthetic glucocorticoid dexamethasone markedly decreases the invasiveness of HT-1080 human fibrosarcoma cells. We show here that dexamethasone treatment of HT-1080 cell aggregates more than doubles their cohesivity from 3.9 to 9.7 dyne/cm. Western blot analysis shows a corresponding increase in cadherin expression. This was accompanied by an increase in the rate of calcium-dependent aggregation. Dexamethasone-treated aggregates spread to form a monolayer in Matrigel spreading assays, but the cells remained much more contiguous than their untreated counterparts. Invasion-suppression by dexamethasone may therefore be due, at least in part, to a previously unsuspected increase in cadherin-mediated cohesion.