The polymorphonuclear leukocyte secretes both O2- and H2O2 when stimulated by various soluble or particulate stimuli. Since a reaction involving iron, O2-, and H2O2 could generate the hydroxyl radical (HO.) there has been speculation that the HO. may participate in the bactericidal activity of the neutrophil. A variety of water-soluble HO. scavengers have been used to test for the participation of HO. and the results imply that HO. might participate. However, other workers have not been able to detect the formation of significant amounts of HO. by the activated neutrophil. We have examined the effect of several commonly used HO. radical scavengers on the ability of the neutrophil to secrete O2- and H2O2. Several of these compounds actively inhibit secretion without affecting the viability of the neutrophil. After considering the various complications inherent in using water soluble radical scavengers, we suggest that they only be used with well defined experimental systems.