Three different murine tumors, CT26 colon adenocarcinoma, Lewis lung carcinoma, and B16 amelanotic melanoma, were injected into syngeneic mice (BALB/c and C57BL/6J) to test the effect of rabbit anti-mouse platelet antibody on the development of pulmonary metastases. Antiplatelet antibody, when injected i.p., decreased the platelet count from 1.5 x 10(6)/microliters to 0.12 x 10(6)/microliters at 6 hr, which remained at this level for 24 hr. Antiplatelet antibody given 6 hr pre- and 18 hr post-i.v. injection of tumor cells decreased the mean number of CT26 tumor nodules per lung by 57% (range, 47 to 65%) and decreased the mean nodule volume of tumor per lung by 37% (range, 0 to 71%) (124 experimental animals), when compared to the effect of nonimmune serum or irrelevant anti-immunoglobulin antibody in 136 control animals. With Lewis lung carcinoma, antiplatelet antibody decreased the mean number of tumor nodules by 62% (range, 57 to 78%) and decreased the mean nodule volume of tumors by 64% (range, 60 to 77%) using 48 experimental animals and 65 control animals. When tumor cells were given s.c., antiplatelet antibody given 6 hr pre-injection, 18 hr post-injection, and every 48 hr thereafter also decreased the mean number of metastases by 42% in 14 experimental and 15 control animals. With B16 amelanotic melanoma, antiplatelet antibody given 6 hr pre- and 18 hr post-injection decreased the mean number of tumor nodules by 85% and decreased the mean nodule volume of tumors by 66% using 9 experimental and 9 control animals. Similar results were obtained when all three tumors were injected 6 hr after the injection of antiplatelet antibody. However, negative results were obtained if antiplatelet antibody was injected 6 hr after the injection of tumor cells. Since antiplatelet antibody has its maximum effect at 6 hr, it is likely that platelets play their role in the development of pulmonary metastases during the first 12 hr of tumor inoculation.