Mycobacterial infections in the transplant recipient differ considerably from those occurring in the normal host. The incidences of active disease, atypical disease, and extrapulmonary disease, especially dissemination, are all increased. These differences are reflected clinically in an increased mortality (30%) and a high rate (37%) of infection associated with rejection. The clinician must rely on sparse data to draw conclusions regarding prophylaxis and therapy. In general, cyclosporine-related drug interactions must be constantly monitored. Pyrazinamide should replace rifampin whenever cyclosporine is in use. Prompt recognition of the diverse presentations of mycobacterial disease and definitive diagnosis and treatment will improve outcome.