Background - Dogs and humans with atopic dermatitis (AD) are predisposed to colonization and recurrent infection with Staphylococcus spp. Studies in humans suggest that staphylococcus-specific immunoglobulin E (IgE) plays a key role in disease pathogenesis. Few such studies have been undertaken in dogs. Hypothesis/Objectives - The aim of this study was to compare levels of staphylococcus-specific IgE and immunoglobulin G (IgG) in dogs with AD, nonatopic dogs with staphylococcal pyoderma, and nonatopic and noninfected control dogs. Animals - Sera were collected from 108 dogs with AD, 39 nonatopic dogs with staphylococcal pyoderma secondary to different underlying conditions, 67 age-matched nonatopic control dogs, and nine control dogs reared in minimal disease conditions. Methods - Serum Staphylococcus pseudintermedius-specific IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay. Results - Dogs with AD had significantly higher levels of anti-staphylococcal IgE than nonatopic dogs with staphylococcal pyoderma and the two groups of control dogs. Levels of anti-staphylococcal IgG were significantly higher in atopic dogs and nonatopic dogs with pyoderma compared with nonatopic control dogs and control dogs reared in minimal disease conditions, but there was no significant difference in levels of anti-staphylococcal IgG between dogs with AD and nonatopic dogs with pyoderma. Conclusions and clinical importance - A significantly increased IgE response to S. pseudintermedius antigens in atopic dogs suggests an immunopathogenic role for anti-staphylococcal IgE. The finding of elevated IgE and IgG in atopic dogs is also important as a prelude to studies on antigenic specificity and possible correlations with disease phenotype.