Fluconazole is an antifungal agent commonly used in liver transplant patients. In addition to its antifungal activity, it is a potent inhibitor of the liver cytochrome P450 enzymes. These enzymes degrade a wide range of metabolically active compounds including glucocorticoids. In this report, we identify an episode of Addisonian crisis that occurred in a liver transplant patient receiving prednisone immunosuppression after fluconazole was discontinued. We postulate the mechanism for the crisis was a reversal of the fluconazole-induced suppression of the P450 enzymes. The resulting increased activity altered the patient's glucocorticoid metabolism leading to an Addisonian crisis.