To determine the potential role of monocytes (peripheral blood monocytes, PBMs) in the pathogenesis of atopic dermatitis (AD), we investigated whether PBMs from patients with severe AD are primed to generate toxic oxygen metabolites. To induce in vitro superoxide anion (O2-) production, we used either particulate (e.g., opsonized bacteria or zymosan) or soluble (e.g., phorbol esters) stimuli, which allowed us to test two distinct pathways for reduced nicotinamide-adenine dinucleotide phosphate activation. In addition, PBMs from the same patients were also examined for their levels of expression of the low-affinity receptor for IgE, Fc epsilon receptor 2 (CD23). We found that PBMs, but not peripheral blood neutrophils, from patients with AD were primed for O2- production as compared to PBMs from either normal control subjects or patients with allergic rhinitis. These cells also expressed increased levels of CD23, and there was a significant correlation between these two parameters. Since the monocytes infiltrating into the AD lesions bear CD23, our data suggest that in vivo priming of PBMs and increased O2- production may participate in the pathogenesis of this skin disease.