We investigated the effects of photopheresis in systemic sclerosis by analysing its influence on lymphocytes with regard to apoptosis and expression of bcl-2 and fas. Peripheral blood lymphocytes isolated immediately before and 24 h after photopheresis were investigated for apoptosis, bcl-2 and fas expression by fluorocytometry, and compared to controls. In addition, leucocytes from systemic sclerosis patients taken directly from the photopheresis system were tested for apoptosis after 24 h in culture. fas expression was similar in controls and patients with systemic sclerosis just before photopheresis, but increased 24 h after photopheresis, mainly due to an increase of CD4+CD95+ cells. bcl-2 was overexpressed in scleroderma peripheral lymphocytes, but not influenced by photopheresis. As compared to healthy controls, the percentage of apoptotic cells 24 h after photopheresis was high in cultured lymphocytes, but not ex vivo. The significant increase in fas on peripheral lymphocytes observed in this study may be a major operative mechanism of photopheresis in addition to (and possibly related to) the induction of apoptosis.