BACKGROUND: Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein. OBJECTIVES: To determine if patients with active psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies. METHODS: Blood was collected from 14 patients with psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of the UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titres using recombinant purified psoriasin and overlapping peptides. RESULTS: We confirmed strong and specific expression of psoriasin in psoriatic epidermis by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean 213 ng mL(-1)) than in controls (mean 331 ng mL(-1), P = 0.308) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with psoriasis and healthy normal donors (mean 0.347 vs. 0.255 units, P = 0.246). The epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity. CONCLUSIONS: Although psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasin-specific autoantibodies appear to be promising serum biomarkers for clinical psoriasis.