Extracorporeal photopheresis is an accepted method for the treatment of cutaneous T-cell lymphoma and much progress has recently been achieved in therapy and understanding of its mechanism. In general large numbers of white blood cells are collected by a cell separator and irradiated in the presence of 8-MOP. In contrast to this practice, data from an animal model showed that as few as 0.2% of the body's blood volume irradiated are sufficient to achieve an immune response after photopheresis. Based on these data we developed a small-scale photopheresis procedure and applied the method in 3 end-stage T-cell lymphoma patients who were not eligible for apheresis. The mononuclear cells from 50 ml of blood were separated by density gradient centrifugation, irradiated with UV-light in the presence of 8-Methoxy-Psoralen (MOP) with 2J/cm(2) and reinjected. 2-3 treatments per week were conducted. The three patients-2 male and 1 female, age 63-86, Sezary syndrome (1x) and mycosis fungoides in tumour stage (2x)-showed no side effects on cell injection. The two patients with mycosis fungoides showed a prompt regression and softening of the tumours. The patient with Sezary syndrome developed numerous necrotic spots on the skin after 6 weeks of therapy that turned normal within a few days. Patient 1 died of pneumonia 4 weeks after the start of therapy and patient 3 died of heart failure 8 weeks after start of therapy, both during regression of the tumours. Patient 2 was treated over a period of 11 months, with an initial regression in the first weeks followed by a slow progression of the tumours after she rejected any form of further treatment. The small-scale extracorporeal photopheresis therapy presented is effective in cutaneous T-cell lymphoma. But questions regarding the optimal number of cells irradiated per treatment, the conditions of cell incubation after irradiation and the number of treatment cycles are still open. Therefore further studies are required to establish a method that is effective and circumvents the use of apheresis technology.