It is critical to determine the status of the immune system in transplant recipients, but there are currently no clinical methods available to do so. To address this, we have developed an innovative method to evaluate the effects of immunosuppressants that involves measuring phytohemagglutinin (PHA)-stimulated cytokine secretions in vitro in response to treatments with dexamethasone (DEX), FK506 or mycophenolic acid (MPA). The results revealed that DEX nonspecifically and dose-dependently inhibited the production of 12 cytokines (IL-2, IFN-gamma, TNF-alpha, IL-8, IL-1beta, IL-17, IL-4, IL-5, IL-6, IL-10, IL-13, and G-CSF). In contrast, FK506 and MPA selectively inhibited the secretion of IL-2 and IL-13, and MPA unexpectedly increased the production of IL-1beta. Therefore, different immunosuppressants have distinct cytokine signatures that can be used to determine whether there is under- or over-immunosuppression in transplant recipients. Immunosuppressants could be adjusted according to the cytokine profiles to maximize immunosuppressive effects while minimizing the risk of infection.