Tuberculosis screening and preventive therapy among the homeless has been a challenge because of the lack of coordinated follow-up. Homeless persons at a homeless shelter in inner city New Orleans were screened for tuberculosis infection and referred for follow-up evaluation and preventive therapy. Fifty-two percent of the 104 persons screened completed the initial evaluation. Twenty-two percent of these patients had latent tuberculosis infection. Forty-two percent of infected patients completed the referral and follow-up process. Patients during the second 3 months of the program were twice as likely to complete the initial evaluation, the referral, and the follow-up process as were patients during the first 3 months due to enhanced awareness and increased educational intervention. A competent referral system for homeless persons may be achieved by implementing a single-clinic, on-site tuberculosis screening and follow-up system with the active participation and coordination of state agencies, the medical community, and organizations which operate homeless facilities.