We report on the levels of expression of IL-1 and IL-6 in skin from psoriasis patients. Different approaches were pursued. Initially, the levels of IL-1 beta and IL-6 were measured in suction blister fluid from lesional and uninvolved skin from psoriasis patients, using a sensitive enzyme-linked immunoabsorbent assay (ELISA) and bio-assay. Skin sections were also examined for the presence of IL-1 and IL-6 using IL-1 beta- and IL-6-specific antibodies. Finally, the expression of IL-1 and IL-6 mRNA was determined in cultured keratinocytes (KC) and fibroblasts from psoriasis skin. Suction blister fluid from lesional and uninvolved psoriasis skin and from skin of healthy individuals did not contain detectable levels (greater than 100 pg/ml) of IL-1 beta. Blister fluid from psoriasis lesions contained low but significant levels of IL-6, whereas the serum levels of IL-6 in these patients was undetectable. Using cryostat skin sections and an IL-1 beta-specific monoclonal antibody (MoAb) in an indirect immunoperoxidase technique, a diffuse staining in the entire epidermis was observed in sections of uninvolved skin from psoriasis patients. In cryostat sections of psoriasis lesions, a faint diffuse staining of the epidermis and a pronounced "dot-like" intracellular staining pattern was observed. On the other hand, the same IL-1 beta-specific MoAb showed, in a indirect immunofluorescence technique using unfixed epidermal cells, bright membrane staining in epidermal cell suspensions from psoriasis lesions. Slightly elevated levels of IL-1 beta and IL-1 alpha mRNA were observed in cultured KC from psoriasis lesions as compared to those in normal KC and in the HEp-2 cell line. Very low levels of IL-6 mRNA were expressed in KC from psoriasis lesions and healthy individuals. Fibroblasts from psoriasis lesions expressed extremely low levels of IL-1 alpha and IL-1 beta, but high levels of IL-6 mRNA. The results point to a paradoxical situation in psoriatic skin: blister fluid from psoriasis lesions contains no IL-1 beta, whereas IL-1 beta is overexpressed on the plasma membrane and in the intracellular compartment of epidermal cells. This finding may help in explaining the observed absence of IL-1 in aqueous extracts of psoriatic scales. Because cultured KC from psoriasis lesions express minimal levels of IL-6 mRNA. dermal fibroblasts, probably together with the inflammatory infiltrate, may represent a major source of IL-6 in psoriasis lesions in vivo.