BACKGROUND Although corticosteroids have dramatically altered the prognosis of patients with pemphigus vulgaris, morbidity and mortality from systemic corticosteroid side-effects remains high. High-dose intravenous methylprednisolone has been used successfully in blistering diseases to avoid the complications of long-term orally-administered glucocorticoids. The objective of this study was to compare the effectiveness and side-effects of oral and pulse steroid therapy in the treatment of pemphigus vulgaris. METHODS One hundred and twenty-three patients with pemphigus vulgaris were categorized into two groups of study and control according to the disease severity and patient's preferred method of treatment. The study group included 36 males and 36 females. The control group included 26 males and 25 females. The mean +/- SD age of the two groups was 42.6 +/- 11.9 and 46.9 +/- 12.8 years, respectively. The mean +/- SD duration of the disease was 6.8 +/- 1.1 months in new cases (n = 45) and 25.9 +/- 26.0 months overally in the study group; it was 7.2 +/- 1.8 months in new cases (n = 30) and 28.4 +/- 24.6 months overally in the control group. During the induction phase, we performed pulse therapy with methylprednisolone in three consecutive monthly courses. Each course included 1000 mg intravenous methylprednisolone for 4 days plus 500 mg intravenous cyclophosphamide for 1 day. In this phase, the control group received 1 - 2 mg/kg/day oral prednisolone for 28 days plus 1.5 mg/kg/day azathioprine. All patients were followed for at least 12 months during which period, clinical response, relapse rate, and side-effects were evaluated. RESULTS Pulse intravenous methylprednisolone with cyclophosphamide was generally safe and well-tolerated. Therapeutic responses of skin and mucosal lesions, rates of complete remission and relapse, and major organ-specific complications were similar in both groups. Significant statistical differences existed in total orally-administered prednisolone in one year, admission duration, and annual weight increments between the two groups (P < 0.05). CONCLUSIONS Considering the side-effects of long-term oral steroids, hazards of obesity, and complications of long-term hospitalization, pulse methylprednisolone could be considered in patients who have problems with long-term admissions or with high-dose oral steroid usage, and also in obese patients.