We have interpreted the literature showing left anterior hypoactivation in depression as reflecting a decrease in approach-related motivation and behaviour among depressed subjects. In support of this model, we have previously demonstrated a decreased responsiveness to reward in subclinically depressed dysphoric subjects. The current study was designed to replicate and extend those findings. Clinically depressed subjects who met DSM-IV criteria for major depression were compared to a group of nondepressed control subjects on a verbal memory task under three monetary payoff conditions: neutral, reward, and punishment. Although control subjects changed their pattern of responding in both the reward and punishment conditions, relative to the neutral condition, so as to maximise their earnings, depressed subjects did not do so during reward. The two groups did not differ during the punishment condition. These findings provide additional evidence of a decreased responsiveness to reward in depressed individuals, and are consistent with the hypothesis that the left prefrontal hypoactivation observed in depression reflects a deficit in approach-related behaviour.