Glucocorticoid receptors were studied in leukemic cells from 14 newly diagnosed adults with acute lymphoblastic leukemia. Receptors were found in all cases; total receptor levels ranged from 1,348 to 18,697 sites per cel (median, 7,553). To determine the utility of glucocorticoid receptor levels for predicting response to glucocorticoid therapy, lymphoblasts were studied for receptors on nine occasions, and the patients were then treated with dexamethasone as a single agent. Response to glucocorticoid therapy appeared to correlate with lymphoblast receptor level. Five of six patients with greater than 4,500 total receptor sites per cell responded; all three patients with less than 4,500 receptors failed to respond. Glucocorticoid receptor level did not correlate with response to combination chemotherapy, duration of remission, or survival. Glucocorticoid receptors were studied at the initial presentation and following relapse in five patients. In two patients, the receptor level did not change following therapy; both patients at diagnosis had leukemias resistant to glucocorticoids. Three patients at relapse developed leukemias with lower receptor levels; these patients had leukemias sensitive to glucocorticoids at diagnosis. Our data suggest that the glucocorticoid receptor levels of lymphoblasts may be useful in predicting response to glucocorticoid therapy in adult acute lymphoblastic leukemia. They also suggest that, following relapse, cases initially sensitive to glucocorticoid may develop resistance by selection of cells with fewer receptors.