Dimethyl sulfoxide (DMSO) has been demonstrated to suppress the in vitro microbicidal activity of neutrophils. In addition, this compound has been described as having significant anti-inflammatory activity. These properties have generally been attributed to the effectiveness of this compound as a hydroxyl radical scavenger. However, DMSO can also act as a reductant under certain conditions, yielding its fully oxidized form, dimethyl sulfone (DMSO2), as the product. Therefore, we evaluated the ability of these two compounds to interfere with the production of oxidants other than the hydroxyl radical by stimulated human neutrophils. In a cell-free assay, DMSO was found to quench the oxidant activity of hypochlorous acid. Neither DMSO nor DMSO2 reacted with superoxide, hydrogen peroxide, taurine chloramine, or monochloramine in this system. However, both DMSO and DMSO2 significantly suppressed the production of superoxide, hydrogen peroxide, and hypochlorous acid by human neutrophils stimulated with either phorbol myristate acetate or opsonized zymosan. Neutrophil viability was not reduced by either DMSO or DMSO2. Inhibition of the oxidative function of stimulated neutrophils by DMSO may provide an alternative explanation for the effects of this compound on the microbicidal activity of neutrophils and as an in vivo anti-inflammatory agent.