Four patients infected with human immunodeficiency virus receiving antiretroviral treatment and high doses of methadone (>200 mg/day) presented with several syncopal episodes. A significant prolongation of the QTc interval was detected in all of them, and in 3 patients, > or =1 episode of Torsades de Pointes was recorded. The sequence of events in these cases suggests that high doses of methadone caused QT prolongation and provided the substrate for syncope and Torsades de Pointes.