Treatment of nude mice bearing xenografts of the human malignant glioma U87MG cell line with the steroid hormone antagonist RU486 for 4 weeks resulted in a significant and dose-dependent suppression of tumor volume and weight. Receptor analyses of tumor cytosol preparations demonstrated a single class of high affinity binding sites for dexamethasone, but the absence of receptors for progesterone. RU486 also nullified the stimulatory effect of dexamethasone on proliferation of U87MG cells in vitro. These results indicate that the growth of U87MG human malignant glioma is dependent on corticoids. The antiproliferative effect of RU486 appears to be due to the inhibition of binding of glucocorticoid hormones to their receptor proteins. Our results suggest a new therapy for some brain tumors, such as malignant gliomas based on the steroid hormone antagonist RU486.