Immunoglobulin gene rearrangement analysis is a sensitive method for determining clonality of B cell proliferations. We have examined tissue obtained from five renal and one cardiac allograft recipient with Epstein-Barr virus-associated B cell proliferations for immunoglobulin gene rearrangements. Biopsies from two patients with lesions that were hyperplastic morphologically, polyclonal by cellular immunoglobulin staining, and had diploid karyotypes, had no detectable gene rearrangements and were, therefore, consistent with benign reactive processes. These patients are alive without evidence of disease 37 and 57 months after diagnosis. In a biopsy from one patient with a lesion that was malignant lymphoma morphologically, monoclonal by cellular immunoglobulin staining, and had clonal cytogenetic abnormalities, clonal gene rearrangements were detected in a majority of cells, confirming their neoplastic nature. In biopsies from an intermediate group of three patients with morphologically malignant proliferations that were composed predominantly of a polyclonal population of B cells, clonal gene rearrangements were also found, consistent with early malignant transformation in a subpopulation of cells. These findings confirm the heterogeneity of the posttransplant EBV-associated lymphoproliferative diseases and have significant implications for our understanding of the pathogenesis of EBV-induced infections and related lymphomas.