High-dose megestrol acetate (800 mg/day) was administered to 34 patients as third-line endocrine therapy for metastatic breast cancer after progression on standard-dose megestrol acetate (160 mg/day). Among the 32 evaluable patients, no complete or partial response occurred. Ten patients remained stable and 22 progressed. No patients remained on study. Median time to progression was 2 months (range, 1-13 months). The use of high-dose megestrol acetate did not result in objective responses but may have been effective in delaying progression in one third of patients.