Activation of the T-cell antigen receptor (TCR) is a key event in triggering the physiological responses of T lymphocytes to antigen. The earliest TCR-evoked signalling steps, such as tyrosine phosphorylations, ras activation and induction of Ca(2+) fluxes, are initiated in the T-cell plasma membrane. It has been implicated that cholesterol- and sphingolipid-rich membrane domains, termed lipid rafts, form platforms for the regulation and transduction of TCR signals at the plasma membrane; however, recent experiments have now differentiated distinct roles for lipid-raft-mediated and protein-mediated interactions in the formation of TCR signalling membrane domains.