The effect of dexamethasone, a synthetic glucocorticoid, on in vitro and in vivo growth and differentiation of the human chondrosarcoma cell line (OUMS-27) was studied. Cells were treated with various doses of dexamethasone, and increasing doses produced an inhibitory effect on OUMS-27 tumor cell proliferation and induced maturation. Cell counts for OUMS-27 on day 9 ranged from 59% of the control at 10-8 M to 45% of the control at 10-5 M dexamethasone. Northern blot analysis revealed that the type II collagen mRNA level in cells given dexamethasone was lower than that in the controls, and the type X collagen mRNA level was higher than that in the controls. Phase-contrast microscopy revealed that cells grown in control medium formed monolayers consisting of small, polygonal cells, whereas dexamethasone-treated cells became larger and more irregular in shape. In the in vivo study the growth rate of masses in nude mice indused by inoculating OUMS-27 cells was also reduced in a dosedependent manner with dexamethasone administration. These results suggest that dexamethasone caused growth inhibition and induced chondrogenic maturation of human chondrosarcoma cells.