The effects of medroxyprogesterone acetate (MPA) therapy on advanced or recurrent breast cancer and its influence on blood coagulation and the fibrinolytic system were compared among three different therapy regimens consisting of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) + MPA and CAF or MPA alone. A clinical response was observed in 42.9% (9/21) of the patients for CAF + MPA, 36.4% (8/22) for CAF and 23.8% (5/21) for MPA alone. No marked thrombosis or its prodromal condition was observed in any group. The effects on the test values for blood coagulation and the fibrinolytic system did not significantly change in the CAF group. However, both AT-III and protein C significantly increased above the normal ranges in the CAF+MPA and MPA groups. Increases in factor X, plasminogen, and alpha 2-plasmin inhibitor/plasmin complex (PIC) and decreases in fibrinogen, tissue plasminogen activator, and D-dimer, were all observed in the MPA and CAF + MPA groups, especially in the MPA group, although these changes remained within the normal ranges. The data indicated that MPA has various influences on blood coagulation and the fibrinolytic system, but these changes did not suggest activation of the blood coagulation system.