Lipoproteins of Mycobacterium tuberculosis (M. tuberculosis) represent an important class of cell envelop proteins. On the whole, 99 putative lipoproteins have been identified in the genome of M. tuberculosis. Earlier investigations on individual mycobacterial lipoproteins demonstrate that some lipoproteins elicit a strong immune response, while others are virulence factors in different models of infection. LpqS is an uncharacterized lipoprotein encoded by the open reading frame Rv0847 of M. tuberculosis. In the present study, we have characterized this putative lipoprotein LpqS with respect to the virulence of M. tuberculosis. A mutant of the M. tuberculosis H37Rv strain not producing LpqS (ΔlpqS) was generated by specialized transduction. The deletion mutant showed reduced growth in Sauton's minimal media and was highly sensitive to SDS and copper, compared to the wild type when grown on solid media. In vitro infection studies showed that the mutant was attenuated for growth in PMA-activated THP-1 cells. Complementation of the mutant with a single copy of the gene cloned under the hsp60 promoter partially restored the phenotype of the wild type strain H37Rv. Thus lpqS plays an important role in sensing the host macrophage environment and might be required for the intracellular survival of M. tuberculosis. Cotranscription of lpqS with the genes downstream cysK2, Rv0849 and Rv0850 was also demonstrated by Reverse transcription PCR (RT-PCR) of intergenic regions.