The proliferative responses of peripheral blood mononuclear cells from ten patients with cutaneous T-cell lymphoma were tested after stimulation with a variety of mitogens, including phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), staphylococcal protein A (SPA), and lymphocyte-conditioned medium (LyCM). Responses were measured by the incorporation of tritiated thymidine and by flow microfluorometry (FMF). In general, responses were depressed, although a broad range of responses were observed ranging from very poor to near normal responses. SPA and PWM were the most potent mitogens in the CTCL patients, unlike controls in whom PHA and SPA were the optimum mitogens and PWM was weakly mitogenic. FMF studies in two patients clearly demonstrated that aneuploid Sezary cells and not admixed normal lymphocytes were proliferating in response to SPA and PWM stimulation. The unusual pattern of mitogen responses found in these CTCL patients suggests Sezary cells may be derived from T-cell subpopulations with special affinity for SPA and PWM. The ability of FMF to demonstrate that aneuploid cells respond to mitogen stimulation makes it a useful additional technique in the evaluation of lymphocyte blastogenesis in patients with malignant lymphoproliferative disorders.