Mangosteen (Garcinia mangostana L.) a tropical fruit, has been used in traditional medicine. A frequently used part of mangosteen is the pericarp, containing a high content of xanthones. a-Mangostin, one of the major xanthone derivatives, exhibits a variety of actions, including antimicrobial, antioxidant, cytotoxic and antitumor; however, its function on the immune system is still equivocal. This study aimed to examine the immunomodulatory activities of a-mangostin on lymphocyte lineage and cytolcine production in human peripheral blood mononuclear cells (PBMCs). The cytotoxic activity of a-mangostin was measured by MTT assay. The concentration of a-mangostin at 5.55 mu g/mL resulted in a 50% survival of PBMCs, which was as potent a cytotoxic activity as that of paclitaxel. After 24 h of PBMCs culture, the percentages of T cells (CD3+), B cells (CD19+) and NK cells (CD3-CD16+CD56+) were not significantly changed by treatment with 1, 2 and 4 mu g/mL of a-mangostin compared with untreated-PBMCs; in addition, the percentages of these lymphocytes treated with the combination of a-mangostin (1, 2 and 4 mu g/mL) and the mitogen concanavalin A (ConA) was not significantly different from that of ConA-treated PBMCs. For cytokine secretion, a-mangostin (1, 2 and 4 mu g/mL) did not significantly induce either proinfiammatory cytokines (i.e., TNF-alpha and IL-beta )or cytokine of adaptive immunity (i.e., IL-2). The combination of a-mangostin (1, 2 and 4 mu g/mL) and ConA did not significantly alter the relative difference of TNF-a and IL-1 beta compared with ConA-treated PBMCs; however, these combinations could significantly decrease the relative difference of IL-2 compared with ConA-treated PBMCs. These data indicated that alpha-mangosfin was able to inhibit IL-2 release without interfering with human immune cells; therefore, further studies are necessary to investigate its effect on IL-2 production.