It has already been clarified that peripheral blood T-lymphocytes which had been activated with phorbol 12-myristate 13-acetate (PMA) acquired the ability to bind to human gingival fibroblasts (HGF) and that the adherence was mediated by VLA integrins. However, these studies also raised the possibility that molecules other than VLA integrins should be involved in the adherence between T-lymphocytes and HGF. In this study, the possible involvement of CD44, a hyaluronate receptor, in heterotypic cell-cell interactions was investigated. It was confirmed that PMA-activated T-lymphocytes strongly adhered to plate-coated hyaluronate and that the hyaluronate binding was clearly inhibited by the addition of OS/37, a newly established mAb specific for the hyaluronate-binding epitope on CD44. Interestingly, OS/37 also blocked the HGF binding of the activated T-lymphocytes when the adherence to HGF was assessed at 4 degrees C, at which temperature the adhesion of integrin molecules diminished, while that of CD44 functioned normally. Immunofluorescence staining revealed that hyaluronate was anchored along the cell surface of HGF. Furthermore, the binding of activated T-lymphocytes to HGF was significantly inhibited by the treatment of HGF with hyaluronidase. These results clearly demonstrated that CD44-hyaluronate interactions participated at least in part in the adhesiveness of T-lymphocytes to HGF.