Extracorporeal photopheresis (ExP) was administered every other week in an outpatient setting to four patients with chronic refractory psoriasis vulgaris without arthropathy. The duration of treatment ranged from six to 13 months. Two patients received methotrexate concomitantly during the initial phase of the study. All patients demonstrated a decrease in erythema, induration, and scaling of lesional skin, accompanied by incomplete clearing of lesions such that the percentage of involvement (SI) ranged between 40 to 80 percent of baseline scores. Exacerbations of psoriasis occurred with minor provocations, and two patients who were predisposed to developing epithelial skin neoplasms as a consequence of prior treatments continued to develop tumors during the study interval. Prolonged ExP treatment was otherwise well tolerated, without evidence of toxicity on routine laboratory safety tests or changes in lymphocyte counts. All patients, however, exhibited decreased intradermal skin responses to recall antigens and a decreased capacity of peripheral lymphocytes to produce interleukin 2 (IL-2) in response to polyclonal stimuli in vitro. These observations suggest that the observed anti-inflammatory effect of alternate-week ExP on psoriasis is mediated in part to a direct inhibition of lymphokine production or release by psoralen-ultraviolet-exposed lymphocytes.