High-dose medroxyprogesterone acetate (HD-MPA) has been successfully employed in the treatment of hormone-related tumors, especially advanced breast cancer. However, progestins in general and MPA in particular are considered a useful treatment also in other types of tumors such as endometrial, prostatic and renal cancer. Furthermore, MPA has been evaluated in tumors which are not classically considered hormone-related, such as ovarian cancer. Therapy with one of a number of progestational agents has been the conventional approach to the management of endometrial carcinoma not amenable to surgery or radiation therapy. Among the various synthetic progestins, MPA has been the most widely employed both by i.m. and oral routes, according to a variety of doses and schedules. Objective responses have been obtained in a percentage of women varying between 30 and 50% in the different series. While the role of MPA in the palliative treatment of advanced disease is well accepted, opinion is divided on the role of progestins in the adjuvant setting. On the basis of available data, it should be concluded that the usefulness of adjuvant therapy with progestins in high risk, early-stage endometrial cancer has not yet been clearly demonstrated. As far as prostatic cancer is concerned, data coming from comparative trials show that MPA is less effective than diethylstilbestrol (DES), and therefore should not be considered the first choice for previously untreated patients. However, it can achieve responses in patients who no longer respond or who are refractory to DES, and represents the treatment of choice for those patients who, due to their cardiovascular conditions, cannot be given estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)