Eight patients with progressive systemic sclerosis were treated with photopheresis or extracorporeal photochemotherapy given on 2 consecutive days every 4 weeks for 5 to 8 months. Previous treatment with immunosuppressive agents or D-penicillamine was discontinued for at least 4 weeks prior to photopheresis. Although IL-2 receptor density in peripheral blood T-lymphocytes decreased significantly in the initial phase of the photopheresis therapy, no substantial clinical improvement occurred. Although the intention had been to treat all patients for at least 8 months with photopheresis alone, it was mandatory due to severe exacerbations to give additional immunotherapy to 4 patients, and 2 of these together with another patient wanted to discontinue photopheresis after 5 and 6 months, as they did not expect an effect. Three of the 4 patients with progression had RNP-antibodies, suggesting that they had their scleroderma as part of a mixed connective tissue disease. The clinical exacerbations were accompanied in all patients by a highly significant increase in serum aminoterminal propeptide of type III procollagen (PIIINP), which has been reported to correlate with involvement of skin and internal organs in systemic sclerosis. Similar but less significant increases were found in serum carboxyterminal propeptide of type I procollagen (PICP); there were no significant changes in serum cross-linked fragment of type I collagen. Plasma levels of 8-methoxypsoralen were all above 80 ng/l, showing that the lack of responses to photopheresis could not be due to poor absorption of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)