Overproduction of interleukin (IL)-6 plays an important role in the pathophysiology of myasthenia gravis (MG), and thymectomy can cause myasthenic crisis because of surgically induced overproduction of IL-6. Preoperative steroid therapy is beneficial in preventing MG crisis during the perioperative period. The purpose of this study was to clarify the effect of preoperative steroid therapy on proinflammatory mediators during the perioperative period of transsternal thymectomy for MG. The study group comprised 20 consecutive MG patients undergoing transsternal thymectomy during the period March 2002 through March 2004. Seventeen of these patients received dose-escalated steroid therapy before thymectomy (steroid treatment group) and three did not (non-steroid treatment group). Serum concentrations of C-reactive protein (CRP) and IL-6 were determined during the perioperative period; clinical outcomes were reviewed, and the results were compared between the two groups. Peak serum IL-6 and CRP concentrations were significantly lower in the steroid treatment group than in the non-steroid treatment group. Amongst perioperative variables subjected to multiple regression analysis, preoperative steroid treatment were found to be the most significant independent predictor of inhibited IL-6 production on postoperative day 1. No postoperative respiratory failure occurred in the steroid treatment group, but it did occur in the non-steroid treatment group. Preoperative steroid therapy can ameliorate IL-6 overproduction and may help stabilize the patient's postoperative condition.