Twelve adults with confirmed pulmonary tuberculosis who failed to respond to repeated skin tests with 250 TU of second-strength purified protein derivative of tuberculin were studied using in vivo and in vitro tests of cell-mediated immunity. All but 2 of the patients failed to respond to skin tests with candidin and histoplasmin, and only one could be sensitized with topical applications of dinitrochlorobenzene. The blastogenic response of peripheral blood lymphocytes from these anergic patients, when cultured in the presence of phytohemagglutinin, pokeweed mitogen, and purified protein derivative, was significantly less than that of lymphocytes from tuberculin-positive control patients. During the course of therapy with isoniazid and streptomycin, 6 of the anergic patients converted spontaneously and reacted positively to purified protein derivative. This skin-test conversion was accompanied by a significant increase in the blastogenic response of lymphocytes from the converted patients when cultured with purified protein derivate. Tuberculin anergy in these 12 patients was not associated with progessive, disseminated disease. All patients responded successfully to the primary chemotherapeutic regimen.