Early clinical studies in which glucocorticoids were used alone in the treatment of acute nonlymphocytic leukemia (ANLL) reported a wide range of responses from remission in some patients to dramatic aggravation of the disease in others. In the hopes of identifying those patients likely to derive therapeutic benefit from glucocorticoids, we have studied glucocorticoid receptors and in vitro responses to glucocorticoids in 36 previously untreated adults with ANLL. The leukemic blasts of all patients contained glucocorticoid receptors (range, 4,300 to 28,400 total receptor sites per cell; median, 8,800). These receptors were similar in all respects studied to those from a variety of other normal and malignant tissues. There was little difference between receptor levels among the various French-American-British categories. In vitro responses to glucocorticoid were observed in leukemic blasts of 26 of 28 cases studied. These responses varied from near complete cell killing to stimulation of proliferation. Since the cells of patients with ANLL have about the same number of receptors as do cells from patients with acute lymphoblastic leukemia and these receptors are capable of mediating physiological responses in vitro, it is unlikely that qualitative or quantitative receptor defects underlie the relative resistance to glucocorticoid therapy of ALL compared to acute lymphoblastic leukemia. However, the broad range of in vitro responses and receptor levels suggests that these studies might be useful in identifying those patients with ANLL likely to derive benefit from steroid therapy.