Recently it has been shown that a large population of children with chronic ITP can be identified by Increased serum cytokine levels. The levels of IL-6, IL-1beta, TNF-alpha, GM-CSF, INF-gamma and sIL-2R were measured in 10 children affected with severe chronic ITP by an ELISA before and after methylprednisolone(MO)bolus. Controls were 10 children without inflammatory diseases. Results are expressed as mean±SD. Statistical analysis was performed by Wilcoxon signed rank test. None of the patients had high serum levels of IL-6 and IL-1beta. Only 2 patients had high levels of GM-CSF and INF-gamma. Instead all patients showed high levels of sIL-2R (1267±631 U/ml vs 67.9±17 U/ml) and of TNF-alpha (23.99±23.176 pg/ml vs 6.3±2.6). The patients were good responders to the administration of a single intravenous injection of 15 mg/Kg MP, which was repeated only for 3 consecutive days. At the end of therapy the number of platelets was well above the danger zone (>50,000/μl) in all patients and about half the children maintained a safe platelet count for a minimum of 1 month. Twenty-four hours after termination of therapy the level of TNF-alpha was decreased(6.56±6.8 pg/ml,p=0.014) while the concentration of sIL-2R was not significantly changed (965±357 U/ml,p=0.058). It appears that the fast remission in the platelet count does not parallel a down-regulation of the immunological response. The effectiveness of a powerful antiinflammatory therapy in the treatment of ITP arises the question whether inflammatory processes may play a role, at least in some cases, in the pathophysiology of ITP.