The B cell repertoire was studied in intestinal mononuclear cells from normal individuals and patients with inflammatory bowel disease (IBD) by examining Ig heavy chain variable gene (VH) usage. Using reverse transcription of intestinal mucosal RNA followed by polymerase chain reaction with primers specific for each VH family and a housekeeping gene, a semiquantitative assay of VH family content in RNA samples was developed. While all VH family members were expressed, differences in VH usage in lamina propria intestinal B cells were noted between Crohn's disease, ulcerative colitis, and normal individuals. mRNA transcripts for VH4 were present at seemingly higher levels than their genomic representation and transcripts for VH1 and VH4 appeared to have higher levels in active, compared to inactive, IBD. Thus, within the massive polyclonal intestinal B cell response, there is a skewed VH usage which may be relevant to the antigenic and/or autoimmune response noted in IBD.