We studied the immunophenotype and the functional reactivity to cytokines of blood cells from eight patients with Splenic Lymphoma with Villous Lymphocytes (SLVL). Cells from all cases exhibited moderate to high levels of membrane immunoglobulin, CD22 and CD40 antigens and light chain restriction (kappa/lambda: 1.7/1). CD44, CD54 and CD11b expression was detected in all cases whereas CD11c was expressed in only four cases (50%). CD11c+ cells lacked CD21 and CD23 expression whereas CD11c cells expressed both these antigens. Cells from most patients (7/8) responded to IL2 whereas only four responded to IL4 and three to TNF alpha. The response to TNF alpha correlated with spontaneous TNF-RII and CD11c expression. Although two days of culture induced the TNF-RII expression in CD11c cells, they remained unresponsive to TNF alpha. These two groups of SLVL patients also differed by IL10 mRNA content: the former (CD11c+, TNF-RII+) contained TNF alpha and IL10 mRNA whereas the latter (CD11c, TNF-RII) lacked IL10 mRNA, even after two days of culture. There were thus two groups of SLVL patients: CD11c+ and CD11c, exhibiting different patterns of cytokine response and production. These groups may correspond to different cell origins or different progression stages of the disease.