The role of cytomegalovirus infection in allograft injury is controversial. A subgroup of renal graft recipients who had histologically proven late-acute rejection did not respond to conventional anti-rejection therapy (80% graft loss within 1 year). These patients showed an expansion of memory-type CD8 peripheral-blood T cells that expressed interferon-gamma mRNA and an association with clinically symptomless cytomegalovirus infection (82% PCR positive, 42% antigenaemia). Antiviral therapy with ganciclovir resulted in stable improved graft function in 17 of 21 treated patients with cytomegalovirus-associated late-acute rejection. The results underline the clinical relevance of cytomegalovirus-related graft injury and offer a novel therapeutic approach.