The growth of primary embryonic facial mesenchyme cells established from cleft palate sensitive A/J and resistant C57BL/6J (C57) mice is inhibited by glucocorticoid treatment. A reduction in cell number in both A/J and C57 culture is accompanied by a significant decrease in [3H] thymidine incorporation into both acid soluble and insoluble material. No significant changes in total cellular protein or [14C] leucine incorporation were observed in either cell type. A greater reduction in [3H] thymidine incorporation occurs in cells undergoing exponential growth following steroid exposure than in cells approaching stationary growth. In both A/J and C57 cultures the reduction in cell number exhibits a dose-dependent response to dexamethasone; is specific for glucocorticoids; and is dependent upon the concentration of serum in which the cells are maintained. A/J cells show a greater sensitivity to the inhibitory effect of dexamethasone on cell number and thymidine incorporation than comparably treated C57 cells. Specific, high affinity, saturable cytoplasmic receptors for [3H] dexamethasone are present in the maxillary cytosols from which the primary cultures were established. These receptors exhibit binding specificity for glucocorticoids, and have properties which are similar to glucocorticoid receptors identified in other systems. In both cell types, a correlation exists between the degree of growth inhibition or reduction of [3H] thymidine incorporation and the level of glucocorticoid receptors. These results provide evidence for a receptor-mediated set of responses to glucocorticoids in these cells.