A randomized, within-subject, double-blind, inpatient study of the physiological and subjective effects of oral 3,4-methylenedioxymethamphetamine (MDMA) was conducted in human volunteers with previous MDMA experience. Placebo, low (1.0 mg/kg), and high (1.6 mg/kg) doses of oral MDMA were administered in a controlled inpatient setting at least 7 days apart to 6 African American (4 male, 2 female) and 2 white (both male) volunteers (mean [SE] age, 21.1 [0.8] years; weight, 77.2 [7.7] kg). 3,4-Methylenedioxymethamphetamine doses were 46 to 150 mg, in the range of typical recreational doses. Participants completed all sessions without clinically significant adverse events. 3,4-Methylenedioxymethamphetamine produced significant dose-dependent increases in heart rate (highest, 132 bpm), systolic (highest, 171 mm Hg) and diastolic (highest, 102 mm Hg) blood pressure, and subjective responses for energy level, closeness to others, mind racing, heightened senses, and high (evaluated by visual analog scales). Peak effects occurred 1 to 2 hours after dose, with no secondary peak. There were no significant effects on body temperature (measured at tympanic membrane), respiratory rate, or blood oxygen saturation (by pulse oximetry). Although most physiological and subjective parameters were significantly correlated with MDMA plasma concentrations, correlation coefficients were low and clinically insignificant, eliminating the ability to predict effects from single plasma concentrations. These findings suggest that oral MDMA in typical recreational doses produces short-term effects on cardiovascular function and subjective state but that temperature effects may result from interaction with environmental and subject factors.