The present study examined resting heart rate variability (HRV; an index of parasympathetic tone) and heart rate response to the Valsalva maneuver (Valsalva ratio; an index of overall autonomic responsiveness) in 12 repeat users of 3.4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and a matched comparison group of presumed nonusers. HRV and Valsalva ratio were smaller in users than in controls. Three out of 12 MDMA users but no controls had Valsalva ratios below 1.50, the cut-off for autonomic dysfunction. In several users, there was a total absence of post-Valsalva release bradycardia. All MDMA users were polydrug users. Parasympathetic cardiovascular tone appears impaired in repeat MDMA users, although the ubiquitous problems in such epidemiologic designs (including lack of testing before the first use of the drug and confounding with use of other drugs) preclude definitive causal interpretations.