Heparinized platelet-rich plasma from 16 normal donors has been examined for platelet aggregation in response to 6 cultured human tumor cell lines. All donors showed maximal aggregation equal to 10 μM ADP with U87MG (glioblastoma) with the exception of one donor (#7) who gave 50% response: donor 7 reacted with no other tumor cell line. With Hut 20 (large cell lung carcinoma, 105 cells/ml) six donors (#3, 4, 7, 14, 15 and 16) failed to show aggregation. With HT 29 (adenocarcinoma, 106 cells/ml), the same six donors (#3, 4, 7, 14, 15 and 16) plus three additional donors (#5, 9 and 10) failed to show aggregation with Hut 28 (mesothelioma) and SKNMC (neuroblastoma), the same nine donors (#3, 4, 5, 7, 9, 10, 14, 15 and 16) failed to show platelet aggregation at 5 × 106 cells/ml. None of the donors showed aggregation with the A549 line (epithelial lung carcinoma). Gel-filtered platelets show no aggregation response with any cell line. Crossover studies with responders and non-responders showed no differences in the platelets from different donors but did show that the aggregation response is dependent upon a plasma component. Interaction of platelets and tumor cells is thought to be an important factor in the metastatic dissemination of human cancer. Similar tumors are known to show different degrees of metastatic activity in different patients. The present results suggest that responders and non-respondiers may be identified from aggregation data and that this differentiation may depend on the presence of unidentified plasma factor(s).