The clinical, histological and immunological effects of long-term treatment with thymopentin (TP-5), administered 50 mg i.v. three times a week on alternate days, in four patients with Sézary syndrome is reported. In all four cases reduction of itching, oedema, scaling and thickening, and clearing of erythroderma were noted after 2 months treatment. Peripheral blood Sézary cells decreased in three cases. Reduction or suspension of the drug was followed by a clinical relapse. A loss of epidermotropism and a reduction in cell infiltrates were observed together with a dramatic reduction in epidermal and dermal Langerhans cells. An increase in the proliferative response to mitogens and in IFN-gamma production, and the expression of activation antigens in PHA stimulated cultures occurred after 3 months. HNK-I+ cells increased both in the peripheral blood and in the dermis following a transient increase in IL-2 receptors, suggesting that clinical response in TP-5 treated patients may be mediated by an increased production of IL-2 and consequent generation of cytotoxic cells or release of lymphokines able to augment NK activity.