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Background: Extracorporeal photochemotherapy has been proven effective in selected T-cell mediated diseases. Aim: To evaluate the safety and efficacy of extracorporeal photochemotherapy in patients with steroid-dependent Crohn’s disease by an open, monocentric trial in three phases of 24 weeks each. Methods: In phase 1 standardized steroid tapering was initiated in patients with a history of steroid-dependent Crohn’s disease. Those with a prospectively evaluated maintenance dose of at least 10 mg/day prednisolone continued steroid-withdrawal under the application of extracorporeal photochemotherapy in phase 2. The duration of remission or response was followed during phase 3. Colonic tissue bioptically obtained before and after extracorporeal photochemotherapy was studied by immunofluorescence microscopy for the presence of photoadduct positive cells. Results: Out of 24 patients included in phase 1, 10 entered phase 2 for extracorporeal photochemotherapy. Four subjects achieved remission and four others response. Significant reductions in serum C-reactive protein levels and intestinal permeability were measured, as well as increases in quality of life and plasma adrenocorticotropic hormone levels. No major side-effects were observed. Remission remained stable in three out of four patients during phase 3. In three patients, positive nuclear stainings of photoadducts were detected in colonic mononuclear cells after extracorporeal photochemotherapy. Conclusions: Extracorporeal photochemotherapy represents a safe steroid-sparing approach in patients with Crohn’s disease and is associated with intestinal homing of photopheresed cells. [ABSTRACT FROM AUTHOR]