Sixty-one immunosuppressed renal transplant recipients were systematically screened for virus infections and the findings correlated with their clinical course. Only herpesvirus (cytomegalovirus, herpes simplex and herpes zoster) were consistently isolated. The onset of virus infections could usually be associated with clinical syndromes. Patients without virus infections were usually asymptomatic. The clinical syndrome associated with virus infection consisted of fever, leukopenia and renal allograft rejection. Renal biopsy, performed at the time serum creatinine levels were elevated, revealed classic rejection; most rejections were reversed by increasing the dose of steroids. Patients continued to excrete virus even after antibody response and clinical recovery. Virus infections do not appear to be incidental findings in transplant patients except after recovery when the virus persists in the immune patient. The clear-cut association between virus infection and rejection episodes suggests a pathogenic relationship. The two mechanisms which seem to best explain the relationship are (1) the virus infection acting as an adjuvant and triggering the rejection of the allograft or (2) the allograft rejection activating a latent virus infection.