We present an analysis of the incidence, clinical presentation, and evolution of tuberculosis in heart transplant recipients at a 2,200-bed tertiary care center in Madrid and review the world literature. During a 5-year period (1989-1993), active extrapulmonary tuberculosis was diagnosed in three of the 144 patients who survived heart transplantation, resulting in an incidence of 1.35 cases per 100 heart transplant-years (> 20-fold the national average). The mean age of the patients was 52 years, and two were male. The mean time to development of tuberculosis after transplantation was 76 days (range, 55-102 days). All of the patients had had previous episodes of rejection and infection and had had initially negative tuberculin tests (one converted to positive during therapy). Clinical manifestations were mild or absent in two of the patients, and Mycobacterium tuberculosis was isolated in association with other microorganisms from two patients. All patients were successfully treated with antituberculous chemotherapy while they were receiving immunosuppressants. A severe drug interaction between cyclosporine and rifampin in the first case necessitated withdrawal of rifampin and precluded its use in subsequent patients. During a mean follow-up of 2 years, no recurrence of tuberculosis has been detected in any of the patients. Tuberculosis was diagnosed in a fourth patient before transplantation, which was performed while the patient was receiving antituberculous therapy. Our data support the conclusion that heart transplantation should be considered an unheralded risk factor for tuberculosis, particularly in countries where this disease is prevalent.