Whereas positive feedback is both rewarding and informative, negative feedback can be construed as either punishing (because it is indicative of poor performance) or informative (because it may lead to goal attainment). In this neuroimaging experiment, we highlighted the informational value of negative feedback by intermixing trials with and without feedback. When performance feedback is expected, positive feedback triggers an increase in striatal activity, whereas negative feedback elicits a decrease in striatal activity. We predicted that, in contrast, when feedback receipt is unpredictable, the striatal response to negative feedback would increase. Participants performed a paired-associate learning task during fMRI scanning. In one condition (“blocked feedback”), the receipt of feedback was predictable—participants knew whether or not they would receive feedback for their responses. In another condition (“mixed feedback”), the receipt of feedback was unpredictable—on a random 50% of trials, participants received feedback, and they otherwise received no feedback. Negative feedback in the mixed feedback condition elicited more striatal activity than negative feedback in the blocked feedback condition. In contrast, feedback omission evoked more striatal activity when feedback delivery was expected, compared to when it was unpredictable. This pattern emerged from an increase in caudate activity in response to negative feedback in the mixed feedback condition and a decrease in ventral striatal activity in response to no feedback in this condition. These results suggest that, by emphasizing the informational value of negative feedback, an unpredictable feedback context alters the striatal response to negative feedback and to the omission of feedback.