Cultivation of human blood monocytes on glass gives rise to cells nonspecifically cytotoxic to tumor cells. If the monocytes are cultured on collagen gels with no contact with glass, no such cytotoxic activity is induced. Killing appeared to be extracellular and probably contact dependent. The glass-induced cytotoxic activity was not related to protein content or cell viability. Rather, it appeared that the monocytes cultured on glass differentiated into cells resembling activated macrophages. On the other hand monocytes cultured on collagen differentiated into cells resembling resident tissue macrophages. These observations are compatible with numerous studies carried out in rodents, showing that activated macrophages, and not resident cells, are cytotoxic to tumor cells.