Tumor cell-platelet interactions have been shown to be involved in the process of metastasis. This study characterizes the aggregation of washed platelets induced by the human uterine carcinosarcoma Colo 526. Ultrastructural studies revealed a two-stage process in which the earliest events were the adhesion and degranulation of individual platelets in contact with the tumor cell membrane. The second stage consisted of a wave of aggregation involving all residual platelets. We found that the first stage was initiated by a factor integral to the tumor cell plasma membrane which acted independently of the tumor cell cytoskeleton or metabolic processes. This factor was found to be a glycoprotein or glycolipid with functionally important sialic acid and N-linked carbohydrate residues. The initial stage was not dependent on platelet activation as neither aspirin nor prostacyclin prevented adhesion or degranulation. The second stage was found to be dependent on platelet activation. These results suggest that platelet aggregation induced by Colo 526 involves a distinctive primary stage which is initiated by a factor on the tumor cell plasma membrane resulting in the degranulation and lysis of individual platelets. This process can occur independently of platelet activation or aggregation and thus may have some relevance to the clinical use of platelet antagonists as antimetastatic agents.