Valvular heart disease, inducing valvular regurgitation, has been described in users of drugs such as anorectic agents and ergot derivates. 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") also leads in vitro to the proliferation of cardiac valvular interstitial cells by activation of the 5-hydroxytryptamine 2B receptor. The aim of this study was to determine the occurrence of valvulopathy in young adults taking MDMA. Twenty-nine subjects using or having used MDMA and 29 gender- and age-matched controls were blindly evaluated with echocardiography. Eight subjects (28%) who took MDMA had abnormal echocardiographic results using the United States Food and Drug Administration's criteria for appetite suppressant-induced valvular heart disease, compared with none in the control group (p = 0.0045). Six (21%) subjects had mitral regurgitation of 1/4 and 4 (14%) of > or =2/4, compared with none in the control group (p = 0.002). The mean mitral regurgitant area ratios (jet/atrium) were 12 +/- 9.8% and 5 +/- 1.3%, respectively (p = 0.007). Tricuspid regurgitation > or =2/4 was present in 13 MDMA users (45%) and absent in controls (p <0.001). The mean tricuspid regurgitant area ratios were 19 +/- 9.5% and 9 +/- 4.5%, respectively (p <0.001). Four MDMA users (14%) had mild aortic regurgitation (p = 0.11). Valvular "strands" were present in 6 MDMA users (21%) and in none of the controls (p = 0.02). In conclusion, MDMA may lead to mild to moderate valvular heart disease and valvular strands.