The ability of subcultured human vascular endothelial cells (EC) to provide immune accessory functions for proliferative responses of highly purified allogeneic CD4⁺ and CD8⁺ T cells has been examined. CD4⁺ T cells proliferated in response to IFN-_γ-pretreated EC which expressed class II molecules, but not to untreated EC. CD8⁺ T cells proliferated to MHC class I molecules expressed on both untreated and IFN-_γ-treated EC. Combined populations of CD4⁺ and CD8⁺ T cells showed synergistic, rather than additive, responses to both untreated and IFN-_γ-treated EC. Furthermore, CD8⁺ T cells were able to induce MHC class II expression on endothelial cells and this induction could be inhibited by an anti-IFN-_γ mAb. The synergistic response obtained by co-culturing CD4⁺ and CD8⁺ T cells with vascular EC was completely inhibited by the sameantl-IFN-_γ mAb. These studies suggest that CD4⁺ and CD8⁺ T cells recognise and proliferate to allogeneic MHC molecules expressed by EC. CD4⁺ and CD8⁺responses are synergistic under the conditions tested and this synergism appears to be due to induction of MHC class II antigens on C by IFN-_γ secreted from CD8⁺ T cells.