BACKGROUND: Animal research indicates that the neural substrates of emotion regulation may be persistently altered by early environmental exposures. If similar processes operate in human development then this is significant, as the capacity to regulate emotional states is fundamental to human adaptation. METHODS: We utilised a 22-year longitudinal study to examine the influence of early infant attachment to the mother, a key marker of early experience, on neural regulation of emotional states in young adults. Infant attachment status was measured via objective assessment at 18-months, and the neural underpinnings of the active regulation of affect were studied using fMRI at age 22 years. RESULTS: Infant attachment status at 18-months predicted neural responding during the regulation of positive affect 20-years later. Specifically, while attempting to up-regulate positive emotions, adults who had been insecurely versus securely attached as infants showed greater activation in prefrontal regions involved in cognitive control and reduced co-activation of nucleus accumbens with prefrontal cortex, consistent with relative inefficiency in the neural regulation of positive affect. CONCLUSIONS: Disturbances in the mother-infant relationship may persistently alter the neural circuitry of emotion regulation, with potential implications for adjustment in adulthood.