Salicylate stimulates the oxygen consumption and also induces multiple drug resistance in Mycobacterium tuberculosis. To gain insight into the mechanisms involved in the above observations, a microarray analysis of M. tuberculosis genes in response to salicylate was performed. Salicylate, besides highly inducing the 27 kD gene (Rv0560c) previously identified as highly salicylate-inducible, also caused increased transcription of a range of genes including an open reading frame (Rv0559c) that is located immediately downstream of the 27 kD gene, and some membrane/transmembrane proteins that may serve as potential efflux pumps or porins. Salicylate also caused a general shutdown of transcription and translation and energy production by down-regulating a range of genes involved in RNA and protein synthesis and ATP synthesis. The role of the salicylate-regulated genes in salicylate induced drug resistance and its unique effect on stimulating oxygen consumption in tubercle bacillus is discussed.