RNA editing by adenosine deamination is catalyzed by members of an enzyme family known as adenosine deaminases that act on RNA (ADARs). ADARs can change the structure of RNA by changing an AU base-pair to an IU mismatch. This frequently modifies the function of the encoded protein, and an emerging theme associated with A-to-I mRNA editing is that tissues often regulate the ratio of proteins expressed from edited and unedited mRNAs to fine-tune cellular responses and functions. In mammals, pre-mRNA of receptor proteins involved in neurotransmission, including serotonin receptors and glutamate receptors, are edited. Currently, only a limited number of human ADAR substrates are known, whereas indirect evidence suggests a substantial fraction of all pre-mRNAs being affected. To identify RNAs containing inosine residues, this study used a multi step approach; including (1) inosine-specific base cleavage and RNase T1 digestion, (2) purification of polyA-tailed mRNA, (3) RT w/ T7-polydT primer, (4) probe synthesis and microarray analysis. Using this method it is possible to identify novel targets of A to I editing. Approximately 100 genes showed a significant decrease in two arrays. Future analysis of these targets should reveal the biomedical significance of A-to-I editing.