We used mouse intraepithelial lymphocyte hybridomas (IELH) to study the role of adhesion molecules, especially beta 7 integrins, in the adherence of IELH to intestinal epithelial cells. Unstimulated 9.1 gamma delta IELH cells expressed high levels of CD11a, CD11a/CD18, CD44, and CD45; medium levels of CD45RB and integrin alpha 4; low levels of alpha M290, beta 7, and 33D1; and very low levels of ICAM-1 and VCAM-1. PHA and TGF-beta stimulated IELH cells--but not control BW5147 cells (alpha 4/beta 7 integrin negative fusion partner)--to bind to IEC-18 and CMT-93 intestinal epithelial cells, but not to renal mesangial cells. The binding was partially blocked by mAbs to integrin alpha 4 and/or alpha M290. The two mAbs in combination did not completely block the binding, suggesting that epitopes not recognized by these two mAbs are also involved in binding. The adhesion of 9.1 gamma delta cells to IEC-18 cells was also partially inhibited by mAbs to VCAM-1, LFA-1, and CD44, but not by mAbs CD45 and a control rat IgG. Thus, IELH may be a useful model system with which to study the role of adhesion molecules in the interaction between IEL and intestinal epithelial cells.