PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, stimulated the production of interleukin-1 (IL-1) by human peripheral blood mononuclear cells more efficiently than the production of tumor necrosis factor (TNF). More IL-1 alpha was accumulated in the cells than in the medium fraction, whereas IL-1 beta was distributed evenly into both fractions. PSK stimulated the production of adherent mononuclear cells, in which significantly higher amounts of IL-1 alpha/IL-1 beta were accumulated per cell than in nonadherent cells. Although IL-1 alpha mRNA synthesis (assessed by Reverse Transcriptase-Polymerase Chain Reaction) was slightly enhanced, IL-1 beta mRNA synthesis was not significantly changed by PSK treatment. This suggests that PSK might increase the efficiency of IL-1 mRNA translation or the posttranslational processing of IL-1 protein. Despite potent cytokine-inducing activity, lipopolysaccharide (LPS) did not significantly stimulate the production of adherent cells. These data suggest that PSK and LPS might stimulate mononuclear cells by different mechanisms.