Background: Although allergens have been implicated as aggravating factors in atopic dermatitis (AD), there is little epidemiologic data on the significance of specific IgE. Objective: We sought to compare sensitization to dust mite and fungi between patients with AD and asthmatic and nonasthmatic control subjects. Methods: Total IgE and specific IgE to Dermatophagoides pteronyssinus , Alternaria alternata , Aspergillus fumigatus , Candida albicans , Malassezia furfur, and Trichophyton rubrum were measured in 73 patients with moderate to severe AD. Total IgE and IgE specific for D pteronyssinus , A alternata , and M furfur were also measured in sera from 156 asthmatic and 212 nonasthmatic control subjects. Results: Positive correlations were found between total IgE and IgE antibodies specific for each of the antigens. IgE specific for M furfur was observed more frequently in adults compared with children with AD (P < .01). AD sera had higher levels of total IgE and a higher prevalence of positive sera to D pteronyssinus (95% vs 42% and 17% for subjects with AD, asthmatic subjects, and nonasthmatic subjects, respectively), M furfur (53% vs 1% and 0.5%), and A alternata (49% vs 29% and 18%). Among the sera from subjects allergic to mites, the contribution of IgE specific for D pteronyssinus to the total IgE levels was similar regardless of the clinical status. Conclusions: Our results demonstrate that moderate-to-severe AD is strongly associated with sensitization to dust mite andM furfur (odds ratios, 45.6 and 132 vs pooled control sera). These results suggest that both environmental allergens and colonizing fungi contribute to the severity of disease, which is consistent with the view that mite avoidance and antifungal treatment can be beneficial in the treatment of these patients. (J Allergy Clin Immunol 1999;104:1273-9.)