We have studied the antileukemic effects of cyclosporin-A (CyA) on the cells of a number of human hematopoietic biopsies and established cell lines in vitro. Cya killed the tumor cells but not the nonmalignant control cells from three of four patients with T-lymphocytic leukemia/lymphoma at concentrations comparable to those recommended in clinical long-term immunosuppressive therapy. The leukemic cells from 7 patients with B-type chronic lymphocytic leukemia were insensitive to CyA. The drug was cytostatic and cytolytic to three of five T- lymphoblastic leukemia cell lines tested. With the possible exception of a plasma cell line, all other control cell lines (B-lymphocytic lymphoma, histiocytic lymphoma, fibroblast, and glia cell lines) were resistant to CyA. These observations indicate that CyA or its derivatives may be useful as a highly selective antitumor agent in different T-cell malignancies.