This retrospective single-case study demonstrates the development of tolerance and reresponse to carbamazepine in a patient with coexisting trigeminal neuralgia and manic-depressive illness. After an initial positive response, tolerance to the antinociceptive and psychotropic effects of carbamazepine appeared during treatment, despite increasing doses. As in preclinical studies of contingent tolerance, periods of carbamazepine discontinuation were associated with reresponse following reinstitution. These are the first clinical data interpreted in a contingent tolerance formulation with reresponse following a medication-free interval. Controlled and prospective studies are needed of the reliability and the pathophysiological and therapeutic implications of this phenomenon.