Dimethyl sulfoxide (DMSO) is reported to have antiinflammatory activity in various systems. Since resistance to bacterial infection can be thought of as a specialized type of inflammation, we were interested in determining the effect of DMSO on phagocyte bactericidal activity. The results indicated that in vitro DMSO treatment of human and mouse neutrophils and mononuclear phagocytes caused a dose-dependent inhibition of the killing of Escherichia coli and Listeria monocytogenes. However, pretreatment of mice with DMSO in vivo caused only a slight decrease in the subsequent in vitro bactericidal activity of neutrophils and macrophages from those mice. In addition, repeated injection of mice with a physiologically relevant dosage of DMSO did not enhance the lethality of either E. coli or L. monocytogenes, nor did it affect the clearance of a sublethal Listeria challenge from the spleen and liver. These results suggest that clinical usage of DMSO should not predispose human subjects to bacterial infection.