Right ventricular endomyocardial biopsies were performed in 15 patients with unexplained cardiac dysfunction, and the expression of intercellular adhesion molecule-1 (ICAM-1) on the myocardium was examined using the streptavidin-biotin complex method. Three of 15 patients (20%) had histologic evidence of myocarditis, and 2 of 15 patients (13%) had borderline myocarditis. The patients with biopsy-proven myocarditis received immunosuppressive therapy (prednisolone 60 mg/day). Two of the 3 patients demonstrated a substantial increase (> 10%) in percent fractional shortening and left ventricular ejection fraction during therapy. Subsequent biopsies revealed ongoing myocarditis in 1 patient, and resolved myocarditis in the other. The remaining patient had persistent cardiac dysfunction, but the subsequent biopsy revealed resolving myocarditis. ICAM-1 immunoreactivity was observed on cardiac myocytes, vascular endothelial cells, and interstitial cells of the patients with myocarditis. However, in patients without myocarditis, ICAM-1 immunoreactivity was observed only on vascular endothelial cells and interstitial cells. ICAM-1 immunoreactivity was still observed on cardiac myocytes in the patients with ongoing or resolving myocarditis during immunosuppressive therapy, but was not detected in the patient with resolved myocarditis. This study demonstrates that ICAM-1 is expressed on cardiac myocytes of patients with myocarditis and persistent cardiac dysfunction despite immunosuppressive therapy. The persistent expression of ICAM-1 may cause chronic inflammation of the myocardium.