A practical on-line lymphocytapheresis (LCP) system using a leukapheresis filter (Cellsorba, Asahi Medical Co.) was evaluated in six patients with refractory rheumatoid arthritis. This filter consists of nonwoven fine polyester fiber wound around a porous cylinder. The blood was passed through the polyester fiber at a flow rate of 50 ml/min for 60 min. LCP was carried out once a week in the first month and biweekly in the next 2 months. An average of 98% of the leukocytes that entered the filter (1.27 x 10(10) cells) and 100% of the lymphocytes that entered the filter (3.66 x 10(9) cells) were removed in the first LCP. A total of 96.6% of the platelets and 2.7% of the erythrocytes that entered the filter were also removed. All of the patients showed clinical improvement in morning stiffness, Lansbury articular index, and functional capacity, with no adverse reaction. The number of circulating erythrocytes and platelets and the concentration of various serum components showed no significant change during the treatments. This LCP system required no fresh frozen plasma, albumin, or other blood transfusion. The number of circulating lymphocytes decreased to 65-70% of the pretreatment circulating lymphocyte count at the last procedure, with a decrease in the ratio of Leu3a positive cells to Leu2a positive cells. The proliferative response to phytohemagglutinin and concanavalin A was improved. These data suggest that LCP to remove approximately 3 x 10(9) lymphocytes once a week or biweekly has an immunomodulatory effect.