The effectiveness of low doses of cyclosporine (3 to 5 mg/kg/day) for short-term treatment in 13 patients with severe psoriasis was studied. The psoriasis cleared in 12 of 13 patients within 3 to 4 weeks of treatment, and there was appreciable improvement in the thirteenth patient. No major side effects were observed: two patients showed biochemical evidence of slight transient renal dysfunction and three others had cutaneous infections (two viral and one mycotic). An immunohistologic study showed that the psoriatic plaques contained an infiltrate composed mainly of activated helper T lymphocytes. After 15 days of cyclosporine treatment, CD4+ cells were significantly fewer in the epidermis and dermis, and Langerhans cells were more regularly distributed in the epidermis. Our studies of neutrophil chemotaxis showed that it is not significantly influenced by cyclosporine in vitro but is decreased in vivo.