Recent advances in clarifying the activation mechanisms of the normal immune system have provided the basis for successful experiments concerning the activation of malignant lymphocytes. Such studies with malignant cells, freshly sampled from patients with lymphoproliferative diseases, can be used for pathophysiological considerations, analysis of tumor evolution, classification of malignant subsets, and karyotyping. Of particular interest is the possibility of abrogating the maturation arrest in some clonally-restricted cells. This might lead to therapeutical implications, since the differentiation blockage plays a fundamental role in the clonal expansion and pathogenesis of tumors. Recently, it has been shown that interferon (IFN) can be a potent inducer of various degrees of transformation, differentiation and even proliferation in different subsets of normal and malignant B cells. This may be important in explaining the divergent results of IFN treatment in various malignant B-cell disorders.