Aims Opioids have been implicated in emotion regulation. Opioid users report decreased negative emotional response, but there has been no formal study on the effect of opioid administration on emotional reactivity. The aim of this study was to investigate the effect of methadone on emotional reactivity in methadone-maintained patients. Design Velten's mood induction procedures were used to induce elative and depressive emotional reactions in the subjects. Each group was administered both induction procedures at 0 hour and 3 hours (corresponding with trough and peak plasma methadone concentrations in methadone subjects). Setting A drug treatment clinic with an out-patient methadone maintenance treatment programme. Participants Twenty-one subjects currently on methadone maintenance treatment and 21 controls with no history of opioid dependence. Measurements Emotional reactivity was measured using mood visual analogue scales. Findings At 0 hour, methadone and control subjects showed similar elation (methadone 13.2±3.1 mean±standard error of the mean [SEM], control 14.4±3.7) and depression reactivity (methadone 23.6±5.0, control 25.1±5.0). However, at 3 hours repeated measures showed that methadone subjects had significantly decreased depression reactivity (methadone 18.5±4.6, control 36.7±5.7; P=0.021) and elation reactivity (methadone 4.4±1.9, control 19.0±2.4) compared to controls. Conclusions Opioid addicts on methadone maintenance appear to be less reactive to mood induction at times of peak plasma methadone concentration than non-addict controls; this suggests that methadone blunts both elative and depressive emotional reactivity.