The in vitro effect of Anapsos, a water based extract of the naturally occurring fern Polypodium leucotomos (calagualine), on human leukocyte fractions was investigated. Calagualine inhibited interleukin-2 secretion and concanavalin A (Con A) stimulated proliferation of T-lymphocytes in a concentration dependent manner. In contrast, a greatly enhanced secretion of IL-1 alpha, IL-1 beta and tumor necrosis factor alpha was induced suggesting a stimulation of monocytes and dendritic cells also present in this system. Endotoxin induced stimulation was excluded. Also in the absence of Con A, calagualine stimulated cytokine production. The presented data show for the first time that calagualine exerts an immunomodulating effect on leukocyte fractions, paving the way for further detailed studies related to possible clinical efficacy.