Background: Serotonin and other vasoactive substances play a critical role in the development of carcinoid heart disease, but the exact etiology of the illness is still unknown. Methods: By using immunofluorescence microscopy, we investigated the expression of transforming growth factor-beta (TGF-beta) and the presence of fibrin-stabilizing factor (XIIIalpha) in endomyocardial biopsy specimens of patients with carcinoid heart disease. In addition, the tissue integrity of the specimens was studied by staining for laminin. Results: Both TGF-beta and XIIIalpha co-localized in the endocardium beneath carcinoid plaques: while TGF-beta was found within myocytes, XIIIalpha was detected on the surface of cells in fibrotic lesions stretching out into the tissue. Laminin staining revealed that the integrity of the endocardium was dissolved and that the tissue consisted of hypertrophic and hypotrophic myocytes. Conclusions: The results suggest that the presence of TGF-beta and XIIIalpha in carcinoid heart lesions indicates that endocardial damage induced by serotonin and other vasoactive substances gives rise to an overshooting wound healing process.