Methylation of the N⁶ position of adenosine (m⁶A) is a posttranscriptional modification of RNA with poorly understood prevalence and physiological relevance. The recent discovery that FTO, an obesity risk gene, encodes an m⁶A demethylase implicates m⁶A as an important regulator of physiological processes. Here, we present a method for transcriptome-wide m⁶A localization, which combines m⁶A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq). We use this method to identify mRNAs of 7,676 mammalian genes that contain m⁶A, indicating that m⁶A is a common base modification of mRNA. The m⁶A modification exhibits tissue-specific regulation and is markedly increased throughout brain development. We find that m⁶A sites are enriched near stop codons and in 3′ UTRs, and we uncover an association between m⁶A residues and microRNA-binding sites within 3′ UTRs. These findings provide a resource for identifying transcripts that are substrates for adenosine methylation and reveal insights into the epigenetic regulation of the mammalian transcriptome.