The clinical and laboratory features of 23 patients with a characteristic form of splenic lymphoma with circulating "villous" lymphocytes (SLVL) are described and compared with those of other B cell disorders with preferential splenic involvement. SLVL affects predominantly men in their early 70's and is characterized by gross splenomegaly with little or no lymphadenopathy, presence of monoclonal gammopathy in two thirds of the cases, and infiltration of the peripheral blood by lymphocytes with a characteristic pattern of membrane irregularity. These lymphocytes are often confused with cells from hairy cell leukemia, from which they can be distinguished by a number of morphological features, by having a small cell volume, and by lack of expression of the HC2 and Tac antigens. The bone marrow is easily aspirated in the majority of cases and shows a relatively sparse infiltration. The spleen histology shows predominant white pulp involvement, although infiltration of the red pulp is seen in a small number of cases. The differential diagnosis of SLVL should also include hairy cell leukemia variant, prolymphocytic leukemia, and atypical forms of chronic lymphocytic leukemia.