The WSU-NHL cell line was established from a malignant pleural effusion occurring in a 46-yr-old female with nodular histiocytic (follicular, large cell) lymphoma. The established cells grow in clumps with a doubling time of 57 h. On light microscopy, cells exhibited primitive lymphoblastoid morphologic features with few cytoplasmic blebs. DNA histogram generated by flow cytometry indicated a hypodiploid stemline (0.93). Immunologic study revealed a mature B-cell phenotype with surface and cytoplasmic IgG lambda and reactivity with monoclonal antibodies to B-cell antigens (B1, B4, BL1, BL3, BL4, BL7, HLA-DR, CALLA and Leu-10). The cells were negative for T-cell and myeloid-monocyte antigens as well as Epstein-Barr virus nuclear antigen (EBNA). Cytogenetic analysis revealed 45,XX metaphases with complex abnormalities including t(14;18) (q32;q21). The phorbol ester, 12-O tetradecanoylphorbol 13 acetate (TPA) (1.6 x 10(-8) M) and interferon gamma (IFN-gamma) (500 U/ml) inhibited cell growth and induced differentiation to a more mature phenotype. The WSU-NHL cell line provides a continuous source of cells for molecular and immunologic studies of human lymphoma as well as the regulation of its growth and differentiation by biologic agents.