Adult atopic dermatitis (AD) patients develop severe facial lesions, which sometimes distribute in sun-exposed areas similar to the rash of systemic lupus erythematosus. To declare autoimmunity in the pathogenesis of AD, we investigated serum antinuclear antibody (ANA) in 256 adult AD patients and identified its ligands. A high titer of ANA was found in 31.3% of AD patients and 75% of the ANA showed a homogenous pattern. Sixty-five percent of ANA(+) sera reacted to a 52 kDa protein (p52) in HeLa cell immunoblots. By screening the HeLa cell cDNA expression library with anti-p52 sera, a clearly positive clone was isolated. The sequence of this cDNA was identical to human elongation factor (hEF)-1alpha. The eluate of IgG bound to hEF-1alpha-glutathione S-transferase (GST) fusion protein recognized a band at 52 kDa in a HeLa cell immunoblot, and stained Hep-2 cell nuclei and cytoplasma as reported in hEF-1alpha distribution. The anti-p52 AD sera recognized the hEF-1alpha-GST fusion protein. The anti-hEF-1alpha antibody-positive AD patients were characterized by higher facial involvement and lower white blood cell counts compared with antibody-negative patients. The present results suggest the possible involvement of autoimmunity in the pathogenesis of adult AD.