Extracorporeal photopheresis in psoriasis vulgaris: clinical and immunologic observations. Four patients with chronic refractory plaque-type psoriasis without arthropathy were treated with extracorporeal photopheresis every other week for 6 to 13 months. In patients 1 and 2, methotrexate was administered concomitantly during the initial part of the trial; the dose was gradually tapered and the drug was discontinued by 6 months. Both patients improved to 23% and 62% of baseline values for percentage of body surface involvement, but their disease then flared when maintenance extracorporeal photopheresis was used alone. Substantial improvement again occurred when lower doses of methotrexate were administered with extracorporeal photopheresis. Patients 3 and 4 were treated initially with extracorporeal photopheresis alone and both improved to 50% and 52% of baseline body surface involvement, respectively, after 4 months of treatment. However, their disease flared because of factors unrelated to treatment. Extracorporeal photopheresis was well tolerated by all patients without evidence of overt toxicity. However, prolonged treatment with extracorporeal photopheresis/methotrexate was accompanied by a decrease in skin reactivity to recall antigens and by decreased capacity of lymphocytes to produce interleukin 2 in response to polyclonal stimuli in vitro. These findings indicate that alternate-week extracorporeal photopheresis has a definite but incomplete suppressive effect on psoriasis vulgaris that may be mediated through an effect on lymphokine production by photomodified cells and that the therapeutic effect of extracorporeal photopheresis may be enhanced by concomitant administration of low doses of methotrexate. 