The fungal immunomodulatory proteins (FIPs) are a new protein family identified from several edible and medical mushrooms and play an important role in antitumor, anti-allergy and immunomodulating activities. A gene encoding the FIP-vvo was cloned from the mycelia of Volvariella volvacea and recombinant expressed in the Pichia pastoris expression system. SDS-PAGE, amino acid composition and circular dichroism analyses of the recombinant FIP-vvo (reFIP-vvo) indicated that the gene was correctly and successfully expressed. In vitro assays of biological activities revealed that the reFIP-vvo exhibited similar immunomodulating capacities as native form. The reFIP-vvo significantly stimulated the proliferation of mouse spleen lymphocytes and apparently enhanced the expression level of IFN-gamma released from the mouse splenocytes. Taken together, the FIP-vvo gene from V. volvacea has been integrated into the yeast genome and expressed effectively at a high level (about 410 mg/ L), it was capable of agglutinating sheep and rat red blood cells. The reFIP-vvo possessed very similar biological activities to native FlPs, suggesting its potential application as a food supplement or immunomodulating agent in pharmaceuticals and even medical studies. (C) 2013 Elsevier Inc. All rights reserved.