Background-In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an eVective form of immunomodulation. Aim-To evaluate its eVect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. Methods-A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). Results-The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding diVerences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no diVerence between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no diVerences regarding weight or height, or episodes of infection between the two groups during follow up. Conclusion-Photopheresis does have an eVect in addition to its possible placebo eVect, shown as a weak but significant eVect on the disease process at the onset of type 1 diabetes, an eVect still noted after three years of follow up. (Arch Dis Child 2001;85:149-154)