Epstein-Barr virus (EBV) infection which is common among immunocompromised patients, may lead to life threatening lymphoproliferative diseases. In this study we examined the incidence and serologic status of EBV infection in 116 renal transplant patients including 84 males and 32 females as well as 72 normal volunteers. The time interval between transplantation and sampling was 1 month to 10 years. Twenty-two patients had a history of rejection. All cases were first transplants except for 3 second transplants. Four patients and no normals showed a positive PCR by a qualitative method. VCA IgM was positive in 11/116 patients (0.09%) and 3 of 72 (0.04%) normal volunteers. 99% (115/116) and 98% (65/72) of patients and normal controls were positive for VCA IgG. EA IgG was positive in 36/116 (31%) and 13/72(18%) of patients and normals, respectively. EBNA IgG was positive in 113/116 (97%) and 100% of patients versus normal controls, respectively. In all except one case with a positive VCA IgM there was a history of infectious mononucleosis-like syndrome. According to our previous data in more than 1000 renal transplant patients during more than 10 years, only one case of PTLD has been diagnosed (0.1%) which is lower than that reported. The high incidence of EBV seropositivity may contribute to this low incidence. The rate of EBV seropositivity in renal transplant patients was greater than in the normal population (P = .05). No association was observed between PCR and seropositivity and rejection or the type of treatment. After this study we began routine PCR and antibody testing in all renal transplant patients both pre- and posttransplant to determine the exact rate of reactivation versus primary infection which we plan to evaluate after 2 to 3 years. In conclusion we believe that the best easiest method to detect EBV infection in immunocompromised patients is VCA IgM ELISA; a qualitative PCR alone is not sufficient for this evaluation.