Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV⁺cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV⁺, EBV⁻ cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV⁺, EBV⁺ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 α and β chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).