Transplant renal artery stenosis (TRAS) is a significant cause of graft dysfunction, with no clearly defined aetiology. Evidence suggests a role for cytomegalovirus (CMV) infection in cardiac transplant vasculopathy and in native coronary artery restenosis after angioplasty. We investigated the relationship between CMV infection after renal transplantation and subsequent development of TRAS. Of 917 patients receiving renal transplants at a single centre from 1978 to 1994, 75 had TRAS diagnosed by angiography. Each was paired with a control transplanted patient with no TRAS, matched for age, sex, year of transplant and number of grafts. Incidence of CMV infection between transplantation and the time of diagnosis of TRAS was assessed in both groups, using clinical and serological criteria to assign patients to three groups: definite CMV infection (CMV-DEF), possible infection (CMV-POSS) and no evidence of infection (CMV-NUL). CMV-DEF was significantly more common in TRAS than in controls (36 vs. 12, respectively, p < 0.001) and CMV-NUL was less common (TRAS 15, controls 33). We have previously reported an increased incidence of acute rejection in patients with TRAS. The subset of patients with no rejection episodes also had significantly more CMV-DEF cases in the TRAS group (54%) than in controls (10%) (p = 0.002). The data are consistent with the hypothesis that CMV infection can contribute to the development of TRAS. The relationship between CMV and TRAS did not arise from an excess of anti-rejection treatment in the TRAS group. CMV-induced large-vessel damage in immunosuppressed patients may occur through local infection and the mitogenic actions of viral gene products within cells of the vessel wall.