SummaryThis study has analysed the binding of a series of anti‐CD2 monoclonal antibodies (MoAbs) to T cells in the presence of the sulfated polysaccharide dextran sulfate (2·3 sulfates/monosaccharide, 500 kDa) (DXS) to define the DXS binding site on CD2. The results show that DXS interacts primarily at the T112 epitope. Thus five anti‐CD2 MoAbs which bound to the T112 epitope were inhibited in their binding by DXS. In contrast, seven anti‐CD2 MoAbs that totally inhibited sheep red blood cells (SRBC) rosetting (identifying the T111 epitope) were unaffected in their binding to T cells in the presence of DXS. Three MoAbs which partially inhibited SRBC rosetting and thereby defining only part of the T111 epitope, were also inhibited in their binding by DXS. Consistent with the conclusion that the DXS binding site on CD2 is associated with the T112 epitope was the observation that interaction of DXS with CD2 resulted in augmented binding of the four MoAbs defining the T113 epitope, possibly reflecting an increased expression of the T113 (activation, CD2R) epitope of CD2. Collectively, the data presented support the notion that a natural ligand for the T112 epitope of CD2 will be identified as a sulphated carbohydrate structure.