Ectodermal dysplasia syndromes are associated with varying degrees of cellular immune defects. Two male siblings with anhydritic ectodermal dysplasia (AED) succumbed to generalized atypical tuberculosis infections. The second child had recurrent bacterial infections as well and is the subject of this report. At age 10 years skin anergy to multiple antigens was present when M. intracellulare was isolated from bone marrow, spleen, liver and multiple lymph nodes. Evaluation of immune function included T and B cell enumeration, mitogen and antigen stimulation, MIF production, serum immunoglobulin and specific antibody production, PMN and macrophage phagocytosis, killing and chemotaxis, and lymphocyte interferon production. General anergy and depressed PMN and macrophage chemotaxis varied indirectly with positive responses to antimicrobial therapy. Persistent abnormal responses included no skin test or in vitro lymphocyte response to M. tb or M. intracellulare, abnormal macrophage morphology, poor granulomata formation, and absent interferon (IF) production. Patient lymphocytes failed to produce IF even after contact with normal macrophages. Although normal lymphoid tissue was present at diagnosis, no lymphoid tissue was present at post mortem. Afferent and efferent defects in immune function appear to be responsible for this fatal illness. Further study of this axis in recovery from tuberculosis and in AED may elucidate the primary or secondary nature of such defects.