Ocean acidification, resulting from the dissolution of excess CO2 produced by humans into the ocean, is predicted to impact a broad variety of marine taxa, particularly calcifying animals such as the thecosome (shelled) pteropods. To achieve a better understanding of the mechanisms of pteropod calcification and physiological compensation for high CO2 exposure, we investigated the transcriptomic responses of Clio pyramidata, a cosmopolitan diel migratory thecosome. Individuals were sampled from the Northwest Atlantic in the fall of 2011 and were exposed to ambient (~380 ppm) and end of the century predicted CO2 levels (~800 ppm) and their oxygen consumption was measured. We then used RNA-seq technology to assess transcriptome-wide effects of exposure to elevated CO2. We conducted a de novo assembly of the transcriptome of C. pyramidata, annotated the genes associated with biomineralization, and assessed the differential gene expression patterns. This assembly reveals a number of similarities with other molluscan transcriptomes, and some similar biomineralization genes such as perlucin, calmodulin, regucalcin and SPARC. The results of the differential expression indicate that there is a great deal of natural variability in gene expression and suggest that a few genes putatively associated with biomineralization, particularly perlucin, were up-regulated in the high CO2 treatment. This is the first experiment employing gene expression analysis to investigate the effects of CO2 on a planktonic open-ocean species, providing the first insights into the effects of acidification on these important planktonic calcifiers and suggesting interesting gene families which may prove useful in further ecophysiological, biomaterials and phylogenetic studies. Overall design: Four discrete individuals of Clio pyramidata were exposed to either ambient (~380 ppm) or high (~800 ppm) CO2 for a period of 9-11 hours, for a total of eight samples.