There may be some difficulties to differentiate Behcet's disease (BD), recurrent aphthosis (RA), and herpetic aphthous ulceration, from other mimicking oral disorders. Despite of unexpected sensitivity and responsiveness, the skin pathergy test regarding a non specific hypersensitivity has long been thought as one of auxiliary diagnostic benefits for BD. To determine the potential usefulness and disease specificity of the prick reaction with saliva, a skin prick test with neat and filter-sterilized saliva was performed on the forearm skin of 26 individuals; 10 patients with BD (8 incomplete type without uveitis, 1 complete type, and 1 neurological type), 5 with RA, 3 with herpetic oral aphthosis, 2 with erythema nodosum alone, and 6 healthy controls. We assessed the skin reaction at 48 hours after pricking, and the pricked skin lesions were biopsied and analyzed immunohistologically. Nine of 10 BD patients (90 %) exhibited an indurative erythema at the skin site pricked with self-saliva, whereas 3 of 5 RA patients (60%) were relatively weak reaction. Pricking with filter-sterilized saliva failed to recapitulate any of positive skin reactions, albeit a faint erythematous dot appeared in a few BD patients, implicating the involvement of causative microorganism(s) in oral bacterial flora. Culture of saliva from 3 randomly chosen BD patients revealed numerous streptococcal colonies on Mitis-Salivarius agar. Histology of the pricked skin sites showed perivascular inflammatory infiltrates, composed of CD4+ T cells and CD68+ monocyte/macrophage lineage, a feature consistent with a delayed type hypersensitive reaction. Our results suggested that skin prick test using self-saliva (a new diagnostic pathergy) can be a simple and valuable in vivo diagnostic approach for differentiating BD and RA from other mimicking mucocutaneous diseases. The positive skin prick may be triggered by resident intra-oral microflora, particularly streptococci, and may in part address the underlying immunopathology in BD.