Lipid-laden macrophages, which are predominantly derived from blood monocytes, are present at sites of active multiple sclerosis demyelination and are assumed to be involved in the demyelinating process. These inflammatory cells produce a variety of toxic oxygen metabolites which can mediate host tissue destruction. We measured production of two oxygen metabolites by monocytes and polymorphonuclear leukocytes in MS patients and controls. Stimulated monocytes produced significantly more hydrogen peroxide, superoxide, and chemiluminescence in the MS group than controls. The polymorphonuclear leukocyte, an inflammatory cell that appears to contribute little to MS demyelination, did not demonstrate increased production of toxic oxygen metabolites in the MS patients as compared to controls. These results suggest that blood monocytes in MS patients are primed to produce increased amounts of cytotoxic oxygen metabolites when exposed to inflammatory stimuli.