Trypanosoma brucei develops chronic infection in mammalian hosts due to a sophisticated strategy of antigenic variation of variant surface glycoprotein (VSG) coat to escape antibody-mediated lysis. MicroRNAs are a class of non-coding RNAs with presumed post-transcriptional regulatory activity. Homology based informatic approach is used to identify the microRNA (miRNA) genes of T. brucei and their target mRNAs. Our observation reveals a set of microRNAs targeting mRNAs corresponding to VSGs. Further, a number of miRNA hairpins have been found in clusters of multiple identical copies. The target proteins, 20S proteosome, GM6 and GRESAG 4.2 corresponding to these clustered miRNAs play essential role in trypanosomiasis. These snippets can act as genetic switches modulating host-parasite interaction and provide useful clue toward treatment of trypanosomiasis. (C) 2008 Elsevier Inc. All rights reserved.