The recent outbreaks of multidrug-resistant strains of M. tuberculosis in health care facilities has increased concern over its transmission in health care facilities. Isolation has been recommended for all patients suspected to have tuberculosis even though the feasibility and the cost of this recommendation can be substantial. We have developed a classification tree using clinical and radiographic data from 277 isolation episodes in patients admitted between August 1992 and March 1994 who required isolation for suspicion of tuberculosis. The classification tree was developed with a sensitivity and negative predictive value of 100% by binary recursive partitioning to predict those patients who are unlikely to require isolation. The predictor variables were upper zone disease on chest radiograph, a history of fever, weight loss, and CD4 count. The tree was validated in a separate cohort of 286 isolation episodes between April 1994 and December 1995. In this validation cohort, no erroneous prediction was made of not isolating a patient with active pulmonary tuberculosis. The classification tree had a sensitivity of 100% (95% confidence interval [CI]: 92.5 to 100%), a specificity of 48.1% (95% CI: 43.8 to 52.4%), and a negative predictive value of 100% (95% CI: 98.5 to 100%). We estimate that the use of the tree could have reduced the number of patients requiring isolation by more than 40% without increasing the risk of cross infection.