Medroxyprogesterone acetate plasma levels were measured in advanced cancer patients after multiple PO or IM administration (500, 1000, 2000, 3000, 4000, and 5000 mg/day PO and 500, 1000, 2000 mg/day IM for 30 days). After PO administration, the plasma concentration rises quickly and plateau level is reached in 4-10 days. Discontinuation of the treatment produces a fast decay (t1/2 = 62.4 h) of the drug levels. When medroxyprogesterone acetate is given IM plasma levels, steadily increase and after drug discontinuation no noticeable decay is observed for at least 6 months; plateau plasma levels are about three times higher than after the corresponding PO treatment. Extremely high interpatient variation in bioavailability is present with both administration routes. These data may well rationalize the results of previous clinical trials and will help in planning treatment schedules.