Functional analysis and surface phenotyping using monoclonal antibodies have revealed that malignant T lymphocyte populations in the peripheral blood of patients with Sezary's syndrome resemble the T helper cell populations from normal individuals. In this article we have studied the effects of the immunosuppressive drug cyclosporine A (CsA) on growth, interleukin-2 (IL-2) production, and the induction of IL-2 responsiveness of peripheral blood monocytes (PBMs) from five patients with Sezary's syndrome in vitro, using the lectin phytohemagglutinin (PHA) and the phorbol ester phorbol myristate acetate (PMA) as stimuli. The following results were obtained: PHA-induced cell proliferation was significantly more sensitive to inhibition by CsA than that induced by PMA or a combination of PMA and PHA (P less than .005). Sezary PBMs produced only small amounts of IL-2 in response to PHA. Stimulation with PMA, however, resulted in significant IL-2 production. PMA and PHA, when given in combination, acted synergistically. The low levels of IL-2 production induced by PHA or PMA were more sensitive to CsA- mediated suppression than those induced by a combination of PHA and PMA (75% and 55% suppression, respectively). CsA-mediated growth suppression could be overcome if the cultures were supplemented with appropriate amounts of exogenous IL-2. We conclude from our data, that CsA in Sezary PBMs inhibits T cell growth indirectly as a consequence of suppression of IL-2 growth indirectly as a consequence of suppression of IL-2 production. Moreover, like normal T lymphocytes, Sezary PBMs do not express the IL-2 receptor spontaneously, but can be induced to do so. CsA does not interfere with intracellular events leading to the expression and the biologic function of the IL-2 receptor.