The cluster of differentiation (CD) antigen CD28 is a 44 kDa, disulphide-bonded, homodimeric glycoprotein, which is constitutively expressed on the surface of the majority of T-cells. CD28 is structurally very closely related to another molecule expressed in activated T-cells, CTLA-4. In particular, the hinge region is completely conserved for both molecules. Also CTLA-4 and CD28 were shown to be very similar at the message and at the gene structure level. The corresponding genes co-map on Human chromosome 2q33. Ligation of CD28 by its counter receptor, B7, expressed on the surface of antigen presenting cells, has been shown to induce signals that, in synergy with those derived from engagement of the T-cell receptor by an antigen bound to a major histocompatibilty complex, enhance proliferation and cytokine production. Manipulation of this interaction can have dramatic effects on the outcome of T-cell activation. Considerable research has been done on the CD28/B7 costimulatory pathway. Blocking thereof results in immunosuppression with implications for the treatment of autoimmune diseases, allergy, organ transplantation and graft versus host disease. Activating the CD28/B7 pathway could be useful for including the immune system to recognize and eliminate tumors that evade the immune system.