The purpose of this study was to determine whether lower doses of dexamethasone for treatment of brain tumor edema are as effective as the conventional dose of 16 mg/d. We consecutively executed two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores of 80 or less. In the first series, we compared 8 mg dexamethasone per day versus 16 mg/d; in the second series, 4 mg/d versus 16 mg/d. Standardized evaluation of quality of life and side effects took place at days 0, 7, 28, and 56. We randomized a total of 96 patients and evaluated eighty-nine. The Karnofsky score improved in the 8-mg group, which had improvement of 8.0 +/- 10.1 (mean +/- SD) points at day 7 versus 7.3 +/- 14.2 points in the 16-mg group. In the second series, the 4-mg group had improvement of 6.7 +/- 11.3 points at day 7 and 7.1 +/- 18.2 points at day 28 versus 9.1 +/- 12.4 and 5.6 +/- 18.5 points in the 16-mg group. Toxic effects occurred more frequently in the 16-mg group (p < 0.03). We conclude that administration of 4 mg dexamethasone per day for treatment of brain tumor edema results in the same degree of improvement as does administration of 16 mg/d after 1 week of treatment in patients who have no signs of impending herniation. Toxic effects are dose-dependent and, during a 4-week period, occurred more frequently in patients using 16 mg/d.(ABSTRACT TRUNCATED AT 250 WORDS)