MicroRNAs constitute a growing class of non-coding RNAs that are thought to regulate gene expression via translational repression. microRNAs Eire initially transcribed as several hundred-nucleotide pri-miRNAs and are then processed to similar to 60-nucleotide hairpin pre-miRNAs. We hypothesized that polymorphisms in both pre-miRNA and mature microRNA modify various biological processes by influencing the processing and/or target selection of microRNAs. In the present study, we sequenced 173 human pre-miRNA genome regions in 96 subjects and found 10 polymorphisms in the 10 pre-miRNA hairpin regions. Although most of these polymorphisms seem to have no effect on microRNA processing; we identified a C to A polymorphism in the mature miR-30c-2 sequence. This polymorphism may alter target selection and thus exert profound biological effects. To the best of our knowledge, this is the first report of polymorphisms in pre-miRNAs. (c) 2005 Elsevier Inc. All rights reserved.