The effect of route of immunization on the protective efficacy of BCG against tuberculosis has been investigated. Immunoprotection was monitored by evaluating the bacteria[ burden in the lungs and spleen of mice challenged with Mycobacterium tuberculosis H(37)Rv after BCG immunization by intranasal (i.n.) and subcutaneous (s.c.) routes. Our results showed that as compared to s.c. BCG immunization, intranasal BCG vaccination induces significantly higher immune responses at local level (mediastinal lymph nodes, cervical lymph nodes and lung). Further, i.n. BCG vaccination induced significantly higher reduction in bacteria[ load in the lungs over s.c. BCG vaccination, whereas, the bacilli toad in the spleen was comparable in both the groups. Hence, intranasal vaccination with BCG holds promise for pulmonary tuberculosis. (C) 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.