The properties of human hepatoma cell lines in relation to their ability to aggregate isolated human platelets were investigated because of the possible relevance to tumour metastasis. Mahlavu, HepG2 and SK55 cells were all able to aggregate platelets irreversibly, but required the presence of small amounts of plasma, which could not be replaced by fibrinogen or other common plasma proteins. They also required the presence of Ca2+. The plasma factor was non-dialysable and heat-labile. In the case of Mahlavu cells and SK55 cells the aggregatory activity was released from the cells as a non-dialysable material of high molecular weight. HepG2 cells were required intact and did not release materials which induced platelet aggregation. In all cases the aggregation was inhibited by hirudin. However, the requirements for plasma factors suggested that the material was not thrombin itself.The aggregatory property of all the cells was inhibited by prostacyclin and in the case of Mahlavu and HepG2 cells, to a lesser extent by nitric oxide. Addition of very small numbers of bovine aortic endothelial cells (but not human umbilical cord cells) inhibited the aggregation induced by Mahlavu and HepG2 cells, but not SK55 cells. If the endothelial cells were pre-treated with aspirin, this inhibitory property was abolished, indicating that a cyclo-oxygenase product was the principal agent.