Elevated serum levels of B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and/or a proliferation-inducing ligand (APRIL) are shown in autoimmune diseases. We determined serum levels of BAFF and APRIL, and clinical association in patients with atopic dermatitis (AD). Serum levels of BAFF and APRIL from 35 patients with AD, 25 patients with psoriasis vulgaris, 25 patients with systemic lupus erythematosus and 25 normal healthy subjects were examined by enzyme-linked immunosorbent assay. Serum levels of APRIL, but not BAFF, were significantly elevated in patients with AD than in healthy controls or patients with psoriasis vulgaris. Patients with severe AD exhibited significantly increased APRIL levels compared to patients with moderate AD and mild AD, and serum APRIL levels were significantly decreased after treatment compared with those before treatment. In addition, increased APRIL levels were significantly associated with serum immunoglobulin E levels and blood eosinophil numbers. These results suggest that elevated serum levels of APRIL are associated with disease severity and activity in AD, and APRIL may have an important role in the pathogenesis of AD.