In 1994 a Texas prison containing a population of mentally retarded inmates experienced a large tuberculosis outbreak. Fifteen cases of tuberculosis were identified (8 confirmed by positive cultures for Mycobacterium tuberculosis) and more than 100 inmates became infected. The culture-confirmed patients were infected with an identical strain of tuberculosis as demonstrated by polymerase chain reaction (PCR) based DNA fingerprinting technique. The prison followed standard tuberculosis infection control policies, but these controls were inadequate to prevent tuberculosis transmission in this special population. Two hundred and thirty inmates (119 inmates showing evidence of new tuberculosis infection or active disease and 111 healthy controls) were enrolled in the investigation. Inmate cell assignments, job duties, and educational classes were identified and medical chart reviews were conducted on all inmates. Tuberculosis transmission was associated with residing on the D Wing of the prison (OR = 25·84, P < 0·01), attending school in Classroom A (OR = 8·34, P = 0·01) and working on the prison utility work crew (OR = 2·52, P < 0·01). The index case in the outbreak had been prescribed 6 months of isoniazid (INH) chemoprophylaxis in 1988.