Because of the effectiveness of isoniazid in treating tuberculosis infection, progression to tuberculosis should be largely preventable. Thus, each case of tuberculosis that occurs may be viewed as a "failure" of the prevention system. We studied the reasons for these "failures" at three centers in different geographic areas in the United States. Two hundred seventy-nine patients with bacteriologically confirmed tuberculosis were evaluated by means of a questionnaire. Our results suggest three main reasons for these missed opportunities of tuberculosis prevention. (1) Patients are out of the health care system until they develop tuberculosis. (2) Patients are in the system but are either not screened for tuberculous infection or, if screened, are not offered preventive therapy when it is appropriate. (3) Because of false negative skin test results, screening may be ineffective at the time it is applied. Advances in tuberculosis prevention will require attention to these areas.