Cytomegalovirus (CMV) is the most important opportunistic infection in renal transplant recipients and is associated with an increased risk of rejection. Infection can be acquired post-operatively (from the transplanted organ) or from re-activation of latent disease. To identify risk factors for CMV disease in a pediatric population within 1 yr of renal transplant, and to generate hypotheses for the pathogenesis of CMV disease in this population, a review of all recipients from 1992 to 1998 in a children's hospital in Atlanta, Georgia, was undertaken. Medical records of 73 transplants performed on 72 patients were reviewed: nine (12.7%) of 72 individuals, after 73 procedures developed CMV disease. Median time to onset of CMV disease was 52 days post-transplant (range = 15-95 days). Receipts of mycophenolate mofetil (MMF), demographic factors, and use of cadaveric kidneys were not associated with a significantly elevated risk of CMV disease. Positive donor CMV serostatus was associated with CMV disease (uni-variate relative risk [RR] = 8.52, Fisher's Exact Test [FET] p = 0.010). Patients with transplants in October or November had a higher risk of developing CMV disease (four of 13; 30.8%) than patients transplanted in other months (five of 60, 8.3%); RR = 3.69; p = 0.047, FET). Most transplants of patients who did not develop CMV disease were performed in January through August (48/64; 75.0%); only 25.0% were performed in September through December. In contrast, six of nine (66.7%) transplants in patients who subsequently developed CMV disease were performed in September through December (p = 0.018, FET). Donor CMV-positive serostatus and transplant in October and November continued to be independently associated with an increased risk of CMV disease when controlled for other factors. The association of transplant in October and November with CMV disease in November-January may be related to an increased risk of seasonal community CMV exposure and primary CMV infection during the peak season for CMV circulation, with subsequent immune suppression promoting progression to disease. Alternatively, co-infection with seasonal pathogens after exposure from an infected donor during the period of immune suppression may promote progression from CMV infection to CMV disease. Further studies should be undertaken to explore these and other hypotheses, which may have implications for determination of a need for anti-viral prophylaxis.