1. Mental status changes are often the earliest indication of an untoward complication after transplantation. These may be obvious, such as hallucinations or paranoid delusions, or they may be subtle, appearing as changes in personality or motivation. 2. The three most common categories of neuropsychiatric posttransplant complications include the following: (1) concurrent pathological processes, such as mass lesion; (2) effects of vasoconstriction secondary to immunosuppressive medications; and (3) central nervous system pharmacodynamic effects of the immunosuppressive medications. 3. This differential diagnosis should guide the history as well as the mental status and neurological examinations. Suspected acute processes deserve computed tomography scanning. Magnetic resonance imaging, more sensitive to subtle structural change, should be generally reserved for cases suggesting such chronic change or those in which treatment appears ineffective. 4. Treatment follows the differential diagnosis. Concurrent diagnoses dictate specific treatment, such as in drainage of a subdural hematoma or administration of antibiotics for cerebral abscess. Symptoms referable to vasoconstriction suggest switching the primary immunosuppressive agent. Symptoms suggesting delirium indicate lowering the dosage of immunosuppressive medication, as in the case of generalized seizure, or use of very low-dose antipsychotic medication, as in cases of confusion, amotivational states, or personality changes.