Calaguala, an extract from the fern Polypodium decumanum, has been used to treat psoriasis and related immunological disorders. In an effort to explain Calaguala's medicinal effects the inhibitory activity of the extract in two platelet activating factor (PAF) related models has been investigated. In the first model, PAF was used to induce release of the proteolytic enzyme elastase in human neutrophils. Calaguala inhibited this effect with an IC50 of 0.1 mg/ml. The known PAF antagonist ginkgolide BN 52021 was used as a positive control and had an IC50 of 0.034 mg/ml. In the second model the inhibition of biosynthesis of PAF in neutrophils using lyso-PAF and labeled acetyl-CoA was studied. Also in this assay Calaguala showed a dose-dependent activity, the IC50 being 0.2 mg/ml. Since recent findings have indicated that PAF might be involved in the pathogenesis of psoriasis, it is possible that the activity shown by Calaguala in these PAF assays may contribute to the clinical efficacy of the extract. The PAF induced exocytosis assay was further used to guide the fractionation of the crude extract. From the acetone supernatant the nucleoside adenosine was isolated as an active principle. Pure adenosine dose-dependently inhibited the exocytosis induced by PAF (IC50 = 0.024 µg/ml) but was inactive in the biosynthesis assay. Adenosine is most probably one of the bioactive compounds of Calaguala responsible for its therapeutic properties.