Background: There is a great emphasis on coronary artery involvement in Kawasaki disease (KD) but much less emphasis on the myocardial inflammation during the acute phase. Moreover, the clinical criteria and the biological markers utilized during the febrile days of the disease oversee the importance of a cardiac-specific marker. Some researchers have suggested that the B-type natriuretic peptide (BNP) increases upon KD onset, reflecting a subclinical myocardial dysfunction. Objectives: To evaluate blood concentrations of BNP and NT-proBNP during the acute and subacute phases of KD. Methods: We conducted a prospective study comparing newly diagnosed KD patients to non-KD febrile controls. Blood specimen were collected at presentation, 6-12 hours after IVIG therapy, 1-2 weeks and 2-3 months later, and only upon reenrollment for controls. Results: Forty-there KD and 19 control patients were consecutively enrolled. The mean age was 47.1±34.3 and 62.2±44.9 months respectively (p=NS). Pre-IVIG NT-proBNP was significantly higher in KD than in controls (923.6±1361.7 v.s. 186.2±198.0 ng/l; p<0.001), with no statistical difference for BNP (141.9±227.5 v.s. 59.9±72.4 ng/l; p=0.112). Samples obtained 1-2 weeks and 1-3 months following the acute febrile status, returned to low values, comparable to controls. Conclusion: This preliminary study suggests that NT-proBNP represents a hopeful adjunctive diagnostic method to support myocardial involvement in KD. As coronary artery dilatation may not be detected in all KD patients upon early presentation, this biochemical marker may prove valuable to support the diagnosis. Furthermore, NT-proBNP appears to have a significant advantage over BNP.