Primary effusion lymphoma (PEL) is a novel lymphoma entity consistently infected by HHV-8 that occurs predominantly in immunodeficient patients and is characterized by liquid growth in the serous body cavities. In order to facilitate the understanding of PEL pathogenesis and histogenesis, we have established three PEL cell lines termed CRO-AP/2, CRO-AP/3 and CRO-AP/5. All cell lines have been derived from HIV positive homosexual men affected by PEL with (in the case of CRO-AP/2 and CRO-AP/5) or without (in the case of CRO-AP/3) a previous history of Kaposi's sarcoma. The cell lines are representative of both virologic variants of PEL, i.e. HHV-8+ EBV+ PEL (CRO-AP/2 and CRO-AP/5) and HHV-8+ EBV- PEL (CRO-AP/3). Morphologic and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 are typical of PEL, and include morphology bridging immunoblastic and anaplastic features as well as an indeterminate (non B- non T-cell) phenotype. The B-cell nature of the cell lines is documented by the presence of rearranged immunoglobulin genes. The detailed analysis of the molecular and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 has allowed the identification of recurrent chromosomal abnormalities of PEL and has contributed to the definition of PEL as a lymphoma of post-germinal center, pre-terminally differentiated B-cells.