Malassezia spp., the causative agents of pityriasis versicolor, are members of the normal human cutaneous microflora. Utilizing a combination of both enzyme-linked immunosorbent assay (ELISA) and bioassay, we have investigated the ability of both formalin-preserved and viable Malassezia (serovars A, B and C) to modulate pro-inflammatory cytokine (IL-6, IL-1β and TNF-α) release by human peripheral blood mononuclear cells (PBMNC) in vitro, over a 48-h co-incubation period. The results demonstrated that formalin-preserved Malassezia (serovars A, B and C) at midexponential phase were generally able to induce a pro-inflammatory cytokine response at a yeast cell to PBMNC ratio of 1:1. In addition, the results consistently demonstrated that at a yeast cell to PBMNC ratio of 20:1, formalin-preserved Malassezia, irrespective of serovar, growth phase or PBMNC donor, were capable of significantly (P<0.05) decreasing the release of both immunochemical IL-6 and IL-1β plus bioactive IL-1β and TNF-α below that of unstimulated culture medium control values. This was apparent following 24- and 48-h co-incubation times, where maximal cytokine production was detected after 24 h. Similar results were obtained for the effect of viable Malassezia on pro-inflammatory cytokine release by PBMNC. Our results suggest that a possible inhibitory component, present perhaps within the cell wall of Malassezia, was responsible for this depressive effect on pro-inflammatory cytokine production.