Interferon regulatory factor 2 (IRF-2) is a member of a family of transcriptional factors involved in the modulation of cellular responses to interferons (IFNs) and viral infection as well as in the regulation of cell growth and transformation. Irf2 knockout mice show T helper 1 (Th1) cell development defect and spontaneous development of an inflammatory skin disease. To determine if there are any mutations in IRF2 associated with development of atopic dermatitis (AD), we screened for mutations in the 5' flanking and coding regions of IRF2 in AD patients and control subjects by single-strand conformational polymorphism (SSCP) analysis. We found three mutations in the promoter region ([-829C>T, -830C>T], -684C>T, and -467G>A), one silent mutation in exon 9 (921G>A), and a 10-bp deletion in the 3' untranslated region (1739[ATCCC]8>6). Among them, the -467G allele and the haplotype of the -467G, 921A, and 1739(ATCCC)8 alleles were transmitted preferentially to AD-affected children (P = 0.02 and P = 0.007, respectively). Our data suggest that IRF-2 plays some role in the development of AD in the Japanese population.