Human cells infected with viruses such as herpes simplex virus (HSV) or Epstein–Barr virus (EBV) become susceptible to the lytic action of a distinct population of lymphocytes termed natural killer (NK) cells present in the blood of normal (sero-negative) and sero-positive individuals1,2. Although NK cells probably represent a subset within the T-cell lineage3,4, they are apparently not restricted in their lytic activity by the major histocpmpatibility complex (MHC) determinants as are most cytotoxic T lymphocytes (CTLs; ref. 5), but can potentially lyse a variety of unrelated virus-infected6 or uninfected cultured cells4,7. In studies with murine models, it has been demonstrated that HSV8,9 or murine cytomegalovirus (MCMV) specific10,11 CTLs show the phenomenon of H–2 restriction initially described by Doherty and Zinkernagel with the LCM virus system12, which is that the CTLs and targets must share H–2K or H–2D products. However, studies in man have not demonstrated the existence of HSV- or human cytomegalovirus (HCMV)-specific CTLs showing HLA (human analogue of mouse H–2) restriction in their lytic activity towards virally infected targets. We demonstrate here that T cells from the peripheral blood of patients recently cured of HSV or HCMV infections, when triggered in vitro with specific antigen and grown as long-term cultures in the presence of T-cell growth factor (TCGF), can mediate virus-specific and HLA-restricted lysis of virus-infected targets. We believe this to provide the first evidence that HLA-restricted and virus-specific T-cell mediated cytotoxicity can be demonstrated in human–HSV and HCMV systems. These HSV- or HCMV-specific CTLs could be important in limiting the in vivo spread of the respective viruses and/or in the pathogenesis of the disease caused by them.