During June 1999-March 2002, a total of 16 tuberculosis (TB) cases were reported from Chickasaw County, Mississippi (2000 population: 19,440), corresponding to annual TB incidences of 20.5-27.6 cases per 100,000 population. In comparison, annual TB incidences for Mississippi during the same period decreased from 7.8 to 5.4 cases per 100,000 population. This report summarizes the results of an investigation of the patients and their contacts and demonstrates the need for strategies to increase the proportion of infected contacts that successfully complete treatment for latent TB infection (LTBI).