Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are seen in immunocompromised hosts and in many lymphoid neoplasms associated with immunocompromise. The posttransplantation lymphoproliferative disorders (PT-LPDs) are a heterogeneous group of B-cell neoplasms that arise in the setting of immunosuppressive therapy, and are associated with EBV infection. Whether type A and/or type B EBV are associated with PT-LPDs is unknown. Therefore, we investigated 27 PT-LPD lesions from 22 solid- organ transplant recipients by polymerase chain reaction (PCR) at the EBNA-2 and EBNA-3c loci to detect sequence deletions that distinguish the two EBV families. Another locus, EBER, was examined by single- strand conformation polymorphism analysis (SSCP), in conjunction with direct sequencing in selected cases. Type A EBV was found in 24 of 27 cases (89%) as seen by amplification of the EBNA-2 and EBNA-3c regions. Four different EBER polymorphisms were detected, confirming the presence of different type A EBV isolates among these cases. Three cases were negative for infection by EBV. Surprisingly, despite the immunocompromised state of the hosts, none of the 27 PT-LPD lesions harbored type B EBV. Thus, although type B EBV may commonly infect peripheral blood lymphocytes in immunocompromised individuals, they do not appear to induce readily PT-LPD formation.