A series of in vitro experiments testing the ability of tumor cells to withstand shear stresses typical of the circulation were carried out. Shearing suspensions of B16 murine melanoma cells in either a cone-plate viscometer or a tubing circuit caused loss of viability whose rate increased with increasing shear rate and shear stress. The killing rate did not depend on the ratio of the container area to volume of the viscometers, suggesting that interactions with the bounding surfaces were not responsible for the cell damage. The loss of viability was not due to the action of intracellular products released during shearing. The results show that all the tumor cells examined were considerably more sensitive to shear than any of the blood cellular elements. Fluid shear stresses in the physiological range can kill tumor cells over time intervals of the order of minutes to hours, results very similar to the time courses observed for tumor cell destruction following injection into the circulation in animal models of metastasis.