Human polymorphonuclear neutrophils have been preexposed to activated complement as zymosan-activated serum (ZAS) or to the chemotactic oligopeptide N-formyl methionylphenylalanine (F-Met-Phe). Spontaneous migration and chemotactic responses toward the deactivating and other cytotaxins were monitored after washing and resuspension of cells in cytotaxin-free medium. Two patterns of deactivation were observed. Preexposure of the leukocytes to high doses of ZAS or F-Met-Phe decreased all subsequent migratory responses. Preexposure of the leukocytes to lower doses of ZAS or F-Met-Phe decreased only a subsequent chemotactic response to the deactivating cytotaxin. These results suggest two mechanisms, or components, of chemotactic deactivation.