Histochemical and immunohistochemical investigations were performed on tissue obtained from the right heart side in three patients subjected to valve, replacement operations because of severe carcinoid heart disease. Extensive fibrotic changes were present on the endocardium of the right atrium, the papillary muscles of the tricuspid valve and the leaflets of the tricuspid and pulmonic valves of all patients. The main constituent of the lesions was a stroma with abundant acid mucopolysaccharides and collagen but devoid of stainable elastic components. The lesions were in some areas sharply delineated from the normal endocardium, but often also extended into the endocardium and myocardium. Small to medium sized vessels were demonstrated histochemically in the lesions and confirmed by positive immunoreaction against endothelial and smooth muscle cells. The moderate number of mesenchymal cells within the lesions had immunoreactivity consistent with muscle cells which seemed to have a very low proliferating activity. The histochemical and immunohistochemical techniques used confirmed some earlier observations in carcinoid heart disease but also rendered new information contradicting previous findings. The infiltrative nature of the carcinoid plaque gives a new dimension to the carcinoid heart disease. The etiology still remains obscure and well known growth factors for connective tissue such as platelet derived growth factor (PDGF) do not seem to be directly involved in the process.