The Banff schema for renal transplant pathology was applied to (1) nine specimens with renal posttransplant lymphoproliferative disease (PTLD) documented by Epstein-Barr virus in situ hybridization and analysis for B-cell lineage and (2) nine allograft nephrectomies classified as severe acute rejection (SAR) based on severe tubulitis, T-cell interstitial infiltration, and absence of Epstein-Barr virus. Tubulitis, venulitis, and infiltration of hilar soft tissues was demonstrable in all specimens. Hemorrhagic infarct-type necrosis was universal in SAR, but occurred in only three of the nine PTLD lesions (P < 0.05, Fisher's exact test). Arteritis in extrarenal vessels was more frequent (nine of nine SAR v four of nine PTLD) and severe (eight of nine Banff grade v3 SAR v four of nine Banff grade v1 PTLD) in SAR. Intrarenal arteries entrapped within PTLD showed grade v3 vasculitis in two cases. Expansile interstitial mononuclear infiltrates, nuclear atypia, and serpiginous necrosis were seen only in PTLD (nine of nine cases). It is concluded that the quality of the cellular infiltrate, its expansile nature, and the presence of serpiginous necrosis help distinguish between severe SAR and PTLD. Tubulitis and intimal arteritis, lesions regarded as specific for rejection in the Banff schema, do not have absolute discriminatory value in this clinical setting.