Serologic testing in inflammatory bowel disease provides a unique tool to classify these diseases into more homogeneous groups. Serum markers can also be used to identify common antigenic triggers and specific defects in mucosal immune regulation and cytokine imbalance in different parts of the gastrointestinal tract. ANCA (antineutrophil cytoplasmic antibodies) and ASCA (anti-Saccharomyces cerevisiae antibodies), the most extensively studied serologic markers, have been used to classify ulcerative colitis and Crohn's disease into such groups with certain phenotypic characteristics and responses to treatment. Similar studies have been initiated in indeterminate colitis, and these results will help in the future to define the immunopathogenesis, prognosis, and response to certain treatments in patients with this type of disease.