OBJECTIVE:To determine whether two adults with stress fractures receiving low weekly doses of methotrexate had methotrexate osteopathy. CASE REPORTS:Two adult patients developed features consistent with methotrexate osteopathy while receiving low weekly doses of methotrexate. METHODS:Iliac crest biopsy samples were taken and bone histomorphometry carried out. RESULTS:Symptoms resolved when the methotrexate was discontinued. Bone histology showed changes consistent with osteoblast inhibition by methotrexate. CONCLUSIONS:When given in low doses for prolonged periods, methotrexate may have adverse effects on bone, particularly in post-menopausal women.