A characteristic of lamina propria lymphocytes (LPL) is their low proliferative response to stimuli of the CD3 pathway. β1 integrins were expressed on LPL; however, their functionis unknown. Therefore, we determined whether β1 integrins contribute to T cell responses by providing costimulatory signals. Integrins on CD4+ LPL of controls and patients with inflammatory bowel disease were characterized by flow cytometry. Cells were stimulated by anti‐CD3 or anti‐CD2 antibodies either alone or in combination with a stimulatory β1 integrinantibody (12G10). Proliferation and apoptosis were measured by 3Hthymidine pulsing or flow cytometry. Cytokine mRNA and apoptosis‐related transcripts were quantified by reverse transcriptase‐PCR. We demonstrated that β1 integrin costimulation restored CD3‐induced proliferation of CD4+ LPL and reduced activation‐induced apoptosis. Activation of β1 integrins by addition of 12G10 antibody to CD3‐stimulated cells restored their capacity to express proinflammatory cytokine transcripts. Further, expression of the activated form of β1 integrins was significantly elevated on LPL from inflamed mucosa. These studies demonstrate that β1 integrin costimulation modulates the response of LPL after TCR stimulation. An increased expression of activated β1 integrins on LPL in intestinal inflammation may abolish their unresponsiveness to antigens and perpetuate the inflammatory process.