To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.