Bacterial phospholipase C has been reported to play a role in the pathogenesis of many bacteria. In order to gain a better understanding of the potential role of Mycobacterium tuberculosis phospholipase C in the pathogenesis of human tuberculosis, we investigated the genetic diversity of the four M. tuberculosis phospholipase Gencoding genes (plcA, plcB, plcC, and plcD) resulting from the IS6110 insertion and associated deletion, among 106 clinical isolates obtained from Turkey, by using PCR, Southern hybridization, and DNA sequencing. Two sequenced M. tuberculosis strains, H37Rv and CDC1551, were used as the references in the comparison. Sixty-six (62.3%) of the 106 isolates had an intact plcD gene, and 40 (37.7%) showed an interruption of the gene. Of the latter 40 isolates, 19 (47.5%) had an IS6110 insertion with no associated deletion in the plcD gene, 2 (5%) had an IS6110 insertion and an associated deletion within the plcD gene, 15 (37.5%) had an IS6110 insertion in the plcD gene that was associated with a partial deletion of the plcD gene and its right forward adjacent region, and 4 (10%) had a complete deletion of the plcD gene. The proportions of the isolates with an interrupted plcA, plcB, or plcC gene were 3.8, 1.9, and 3.8%, respectively. The data indicate that there is a much higher frequency of IS6110 insertion and deletion in the plcD gene than in the plcA, plcB, and plcC genes of M. tuberculosis.