BACKGROUND: Iron deposits are characteristic of endometriotic lesions, and pelvic iron concentrations are higher in endometriosis patients than in women without endometriosis. In this study, the effect of iron overload and iron chelation on the development of endometriosis in a murine model was investigated. METHODS: Human menstrual endometrium was injected i.p. into nude mice, either alone (controls) or supplemented with erythrocytes or desferrioxamine (DFO), an iron chelator. After 5 days, the iron load of endometriosis-like lesions and peritoneal macrophages and fluid was evaluated. Lesions were quantified by immunohistochemical morphometry, and their proliferative activity was assessed. RESULTS: Injection of erythrocytes into the pelvic cavity caused iron overload in lesions (P < 0.025) and peritoneal macrophages (P < 0.01) and fluid (P < 0.05), whereas DFO effectively reduced iron status in lesions (P < 0.05) and macrophages (P < 0.01) compared with controls. No difference was observed in the number or surface area of lesions between the three groups. Erythrocytes increased (P < 0.05) and DFO significantly decreased (P < 0.01) the proliferative activity of lesions. CONCLUSIONS: Iron overload does not appear to affect lesion establishment but may contribute to the further growth of endometriosis by promoting cell proliferation of lesions. Iron chelator treatment could therefore be beneficial in endometriosis to prevent iron overload in the pelvic cavity and decrease cellular proliferation of lesions.