Recently we described a new elastase inhibitor (skin-derived antileukoproteinase, SKALP) that is expressed in psoriatic epidermis and cultured keratinocytes, but is virtually absent in normal skin. In this study we investigated whether SKALP activity could be measured in urine of psoriatic patients and healthy controls. We found that urine of psoriatic patients contained considerable amounts of anti-elastase activity, whereas this activity in urine from normals was significantly lower. The properties of the urinary anti-elastase activity in psoriatic patients were indistinguishable from that of epidermal SKALP. It was found to be a cationic, heat-stable protein with an apparent molecular weight of 11 kDa on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and a K(i) of approximately 2 x 10(-11) M. In addition, in Western blotting partially purified inhibitor from urine was found to react with a polyclonal anti-SKALP serum. SKALP in urine was either present in a free form or in a latent form, most likely complexed with elastase. We speculate that SKALP in urine of psoriatic patients is derived from the epidermis, and that it might serve as a marker for disease activity.