Methamphetamine is a widely abused psychostimulant. Abusing methamphetamine causes various adverse effects, such as immune dysfunction. The present study investigated the effect of diazepam, a central depressant, on methamphetamine-induced immunosuppression. BALB/c mice were daily administered with diazepam and methamphetamine (5mg/kg of each), either alone or in combination, for 5 consecutive days followed by sensitization with ovalbumin (OVA). Two days later the same dosing and sensitization regimen was repeated once. The production of serum anti-OVA antibodies, and the cellularity and functional activities of splenocytes were measured 7 days post the 2nd OVA sensitization. The results demonstrated that methamphetamine and/or diazepam significantly attenuated the production of OVA-specific IgM, IgG(1) and IgG(2a). Concordantly, splenocytes of mice administered with diazepam and/or methamphetamine produced less IL-4 and IFN-gamma upon ex vivo re-stimulation with OVA, as compared to the vehicle-treated control. In contrast, the cellularity and metabolic activity of splenocytes were not altered by the drug treatment. These results indicated that the central depressant diazepam did not affect methamphetamine-mediated immunosuppression. Rather, both drugs markedly suppressed antigen-specific antibody production and T-cell reactivity.