The antimetastatic effect of the antithrombotic agents exogenous prostacyclin (PGI2) and a synthetic analog, Iloprost, on experimental metastasis formation was studied by injecting BL6 melanoma cells into C57BL/6 mice. Suitable in vivo treatment conditions were selected according to the known properties of the two drugs, including their pharmacokinetics. Iloprost showed a greater ability to inhibit platelet aggregation induced by BL6 melanoma cells. PGI2 displayed a limited antimetastatic activity, largely dependent on the tumor cell load and treatment schedule. Iloprost showed a far superior activity, its antimetastatic effect lasting longer and remaining detectable up to 6 h after tumor cell inoculation. The present data complex provides further support to the concept of a crucial role for platelet-tumor cell interaction in the process of metastasis formation.