Methylenedioxymethiamphetamine (MDMA; 'Ecstasy') is a widely abused amphetamine derivative. In the present study, we examined the effect of acute MDMA administration on an antigen specific immune response. Responsiveness to an in vivo challenge with the soluble protein antigen keyhole limpet haemocyanin (KLH) was examined in rats following MDMA administration (2.5, 5 or 10 mg/kg; i.p.). KLH-specific serum IgM concentrations were measured 7 days following challenge, and serum IgG concentrations were measured 14 days following the KLH challenge. In addition, antigen-specific IFN-gamma and IL-6 production was measured in kLH-stimulated splenocytes. MDMA did not alter the KLH-specific IgM response. In contrast, MDMA (5 and 10 mg/kg) provoked a significant suppression of KLH-specific IgG production. Thus, MDMA administration did not alter the initial generation of the antibody response but rather inhibited antibody class switching from IgM to IgG. Two pathways for the genetic switch from IgM to IgG production were investigated. One pathway requires the Th, type cytokine IFN-gamma to stimulate IgM-secreting cells to switch to IgG(2a)-secreting cells. Another pathway requires the Th-2 type cytokines IL-4 and IL-6 to stimulate IgM-secreting cells to switch to IgG(1)-secreting cells. IgG, and IgG(2a) levels were measured to determine if these two pathways were differentially affected. The results indicate that only IgG(2a) levels were decreased following MDMA administration. Furthermore, this decrease in IgG, was accompanied by decreased KLH-specific IFN-gamma production 14 days post KLH administration. In conclusion, these data indicate that MDMA alters the ability to switch from IgM to IgG(2a) production, possibly by reducing IFN-gamma. Potential health consequences for MDMA users are discussed. (C) 2001 Elsevier Science BN. All rights reserved.