ASLC is clinically and endoscopically similar to active idiopathic IBD, especially ulcerative colitis. While several histopathologic criteria have been described which are useful in distinguishing these conditions, the diagnosis can still be difficult. In this study, we review the use of immunofluorescence on formalin-fixed paraffin-embedded biopsies from patients with ASLC. While tissues from active IBD have a striking increase in the number of IgG- and a lesser increase in the IgA- and IgM-containing plasma cells in the lamina propria, tissues from ASLC have normal numbers of IgG-containing cells with only a slight increase in IgA- and IgM-containing cells. The use of immunofluorescence on these tissues can provide quantifiable information which may be a helpful diagnostic adjunct in distinguishing these alternatives if histopathologic evaluation is equivocal.