The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compared with effects on mononuclear blood cells from chronic lymphocytic leukemia (CLL) patients and healthy donors. Natural IFN-alpha (nIFN-alpha) induced a proliferative response in cells from seven of 17 of the B-cell lymphomas, in two of eight of the non-malignant lymph nodes, and in lymphoid blood cells from two of 32 CLL patients. With few exceptions, the proliferating cells were B cells and the data suggest that IFN acts directly on the B cells. Proliferation was not induced with IFN in cells from the T-cell lymphoma or in mononuclear blood cells from 13 healthy donors. nIFN-alpha induced blast transformation in cells from ten of 14 of the B-cell lymphomas and in four of seven of the non-malignant lymph nodes. Also beta- and gamma-IFN were shown to induce proliferation and blast transformation in lymph node cells from some patients. No major effect on the expression of various differentiation markers could be observed following culture in the presence of nIFN-alpha. We conclude that IFNs can induce proliferation and blast transformation in malignant and non-malignant B cells from lymph nodes.