Mass spectrometry and peptide-centric approaches are powerful techniques for the identification of differentially expressed proteins. Despite enormous improvements in MS technologies, sample preparation and efficient fractionation of target analytes are still major bottlenecks in MS-based protein analysis. The complexity of tryptically digested whole proteomes needs to be considerably reduced before low abundant proteins can be effectively analysed using MS/MS. Sample preparation strategies that use peptide-specific antibodies are able to reduce the complexity of tryptic digests and lead to a substantial increase in throughput and sensitivity; however, the number of peptide-specific capture reagents is low and consequently immunoaffinity-based approaches are only capable of detecting small sets of protein derived peptides.In this proof-of-principle study, special anti-peptide antibodies are employed to enrich peptides from a complex mixture. These antibodies recognize short amino acid sequences that are found directly at the peptides' termini. The recognised epitopes consist of three or four amino acids only and include the terminally charged group of the peptide. Due to its limited length, antibodies recognising the epitope will enrich not only one peptide, but a whole class of peptides that share this terminal epitope. In this study beta-catenin-derived peptides were used to demonstrate that it is possible (i) to effectively generate antibodies that recognize short c-terminal peptide epitopes and (ii) to enrich and identify peptide classes from a complex mixture using these antibodies in an immunoaffinity MS approach. The expected beta-catenin peptides and a set of 38 epitope-containing peptides were identified from trypsin-digested cell lysates. This might be a first step in the development of proteomics applications that are based on the use of peptide-class specific antibodies.