In this report, the authors review findings from their research into the immunological effects of repeated doses of MDMA in humans (Pacifici et al. 2001), They also present new data comparing immunological function in regular ecstasy users with non-drug using controls (see structured abstracts under "Studies in Ecstasy Users" under the same reference). The reduction in CD4 cells, decreased lymphocyte responsiveness and increase in natural killer (NK) cells produced by an initial dose of MDMA were enhanced and strengthened by a second dose of 100 mg MDMA given 4 hours later. While these immunological changes disappeared at 24 h after a single dose, residual immunological effects were still present 24 h later. When one 100 mg dose was followed by another 100 mg dose 24 h later, the immunological effects of the second dose were all greater than the effect of the first dose, even though immunological parameters had returned to baseline prior to administration of the second dose. MDMA AUC was also 49% greater in the second dose, though rise in cortisol after the second dose did not differ from the rise seen after the first dose. One participant in the second study was a poor metabolizer (perhaps defined through dextorphan/dextromethorphan test). His NK cell count was significantly higher after each dose of MDMA, even though CD4 cells were not significantly lower than those of good metabolizers. His AUC for MDMA was 60% higher, but elevation in cortisol was no higher than that of good metabolizers. A comparison of baseline immune cell counts in a large (probably pooled) sample of male ecstasy users and non-drug using controls found that NK counts were lower in ecstasy users, and that there were trends for lower total lymphocyte counts and CD4 cells. Cell counts from 6 of the 30 ecstasy users were compared with counts from 8 non-drug using controls matched on age, weight and height. Cell counts taken from ecstasy users 1 year after baseline had lower numbers of lymphocytes than controls, and cell counts 2 years after baseline found lower CD4 and B cells samples from ecstasy users. These findings seem to suggest that regular ecstasy use may affect immune function, though given that all ecstasy users were polydrug users, the effects of other drugs may have been overlooked by this comparison. Taken together, it appears that the acute effects of repeated doses of MDMA are not identical to the effects of regular ecstasy use. Findings from the second repeated dose study, and comparisons between one poor metabolizer and the rest of the sample suggest that the immunological effects of MDMA are not strongly associated with cortisol release. It should be noted that this report contained insufficient information on drug use parameters or on consumption of other drugs, so that it is difficult to determine whether reduced immune function was due to ecstasy use or use of other drugs. Since only male participants were studied, it is uncertain whether results are generalizable to women.