Anticoagulation with warfarin is effective in decreasing experimental metastases, presumably by preventing the fibrin coagulum demonstrated to be necessary for the lodging of tumor cells. To determine the optimal level of anticoagulation for maximal antimetastatic effect, 2 similar experiments were completed with a methychloanthrene-induced sarcoma in C57Bl mice. Footpad tumors were produced by tumor cell injection and the mice were divided into 4 equal groups: control, and groups on 1, 2 and 3 mg/l of warfarin, respectively. Control and anticoagulated mice were amputated at the same interval. Three weeks after amputation, all were killed and their metastases were quantitated. Prothrombin times ranged from 10 s in the control to 30 s in the 3 mg/l group. In experiment 1, there was a significant reduction of pulmonary metastases at all levels of anticoagulation. The controls showed a mean number of 7.7 metastases/mouse, as compared to 2.9 (P < 0.002) at 1 mg/l, 2.1 (P < 0.0035) at 2 mg/l and 0.7 (P < 0.002) at 3 mg/l. In experiment 2, the significant effect was found only at the 3 mg/l dose, with those mice having 2.3 metastases/mouse as compared with 5.5 in the controls (P < 0.001). Full anticoagulation in the range of 2.5-3 times normal in required for a maximal antimetastatic effect.