CD98 is a widely expressed cell surface heterodimeric glycoprotein, which is rapidly up-regulated upon activation of T lymphocytes. Monoclonal antibody (mAb) 80A10 recognizes an epitope on CD98 and in combination with CD3 antibody causes proliferation of peripheral blood T lymphocytes. CD98 co-stimulatory activity, mediated by either mAb 80A10 or 4F2, a well-characterized CD98-specific mAb, is blocked in the presence of the soluble beta1 integrin antibody 18D3. Previously we have reported that co-stimulatory activity of antibodies to integrins alpha4beta1, alpha5beta1, alphaLbeta2 and alpha4beta7 is inhibited by 18D3, whereas co-stimulation mediated by non-integrins was unaffected. Thus the non-integrin CD98 is uniquely sensitive to the inhibitory effects of beta1 integrin-blocking antibodies, which may reflect convergent signalling mechanisms between integrins and CD98. This is consistent with recent reports suggesting that CD98 may regulate integrin-mediated adhesive events.