Signals delivered through the T-cell receptor (TCR) by peptides bound to the MHC molecules, antibodies directed against the TCR complex, and mitogenic lectins fail to induce full T-cell activation. In the past decade investigators have shown that to become fully activated, T-cells require both a TCR-generated signal and a'co-stimulatory signal'. Evidence indicates that CD28 provides this necessary signal by regulating a signal transduction pathway distinct from that generated through the TCR [1, 2]. Signalling through CD28 drives cyclosporin-independent T-cell proliferation and cytotoxic activity through the enhanced production of cytokines such as interleukin 2 (IL-2), interferon y (IFN-y), granulocytelmacrophage colony-stimulating factor and tumour necrosis factor c1 (TNF-a), which are up-regulated by both transcriptional and post-transcriptional processes [3-51. Counterreceptors for CD28 are the B7 molecules (CD80 and CD86) that are expressed on B-cells, dendritic cells and macrophages [6-81. These cognate ligands also bind to another T-cell receptor, CTLA4, which is structurally related to CD28. Recent work illustrates that CD28 and CTLA4 have opposing effects on the response of T-cells to stimulation, with CTLA4 inhibiting or downregulating T-cell activation [9, 10]. Thus CD28 has proved to be important to normal immune function and regulation and perhaps has a role in T-cell development [11, 12]. In this paper we summarize recent progress in the understanding of the biological events triggered downstream of CD28 receptor ligation.