A chemotactic factor inactivator (CFI) has been found in extracts of Walker and Novikoff tumor cells maintained in rats. The CFI directly inactivates the bacterial chemotactic factor as well as the leukotactic activity (fro both neutrophils and monocytes) associated with C3 and C5 fragments and with culture fluids of lectin-stimulated lymphoid cells. The inactivation of the bacterial chemotactic factor is temperature and pH dependent. Subcellular fractionation procedures indicate that CFI is largely associated with the microsomal and cytosol fractions of tumor cells. CFI activity is also found in rat neutrophils, alveolar macrophages, and in extracts of liver, spleen, and kidney from normal animals. CFI derived from normal tissues also directly inactivates the bacterial chemotactic factor and has the ability to inactivate chemotactic activity associated with C3 and C5 fragments. A feature of the tumor-associated CFI is its presence in ascitic fluids of animals bearing tumor cells and the relative absence of any CFI activity in acute inflammatory exudates. The finding of the tumor-associated CFI may explain, at least in part, the tendency of malignant tumor cells to suppress cellular inflammatory reactions.