Megestrol acetate (MA) is one of the most widely used progestins in the palliation of advanced breast cancer, but its optimal dose level has yet to be defined. Forty-six women with progressive advanced disease were given MA according to a monthly loading-dose-schedule (320 mg/day orally) followed by standard-dose maintenance (160 mg/day). Most of the patients had been heavily pretreated with endocrine and/or chemotherapy; all the cases were evaluable. The response rate was 20% (95% CI: 9-31%), with 9 subjects achieving PR. The median time to response was 3 months (range 2-11), the median response duration being 3 months (range 3+-12+). After a median follow-up period of 8 months (range 7-16), only 3 of the patients achieving PR are still on treatment. No increased toxicity or potentially detrimental endocrine effects were observed and all of the patients showed good compliance to treatment. Although the loading-dose schedule used in the present series proved to be feasible, it does not appear to provide any clinical advantage over standard-dose MA treatment.