Following heart transplantation remodeling of the donor heart causes changes in the extracellular myocardial matrix. We investigated 20 right ventricular endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group II, n=11) after heart transplantation from 16 patients transplanted for end-stage cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed at a magnification of 400x using a computer-assisted image analyzing system measuring the relative area stained by the immunoperoxidase method, the number of cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9 μm 2 in group I and increased significantly 66+/-13 days after heart transplantation in the perimysium around the myocardial cells as well as in the endocardium to 49.9+/-15.1 μm 2 (P<0.05). No quantitative change in collagen III was noted (75.7+/-12.4 versus 75.5+/-16.0 μm 2 n.s.). Collagen IV was found in the perimysial, in the capillary bed and in the vascular network. Significant quantitative change in the amount of collagen IV was not found (64.1+/-12.6 versus 61.0+/-8.9 μm 2 ). Fibronectin was found in the entire perimysial extracellular matrix and in the endocardium in relationship with collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 μm 2 (group I) to 140.8+/-17.9 μm 2 (group II, P<0.05) was found. The cell area and cell diameters were not significantly different (group I; cell area 772+/-227 μm 2 , diameter 31.3 μm; group II; cell area 776+/-224 μm 2 , diameter 31.4 μm).y It is concluded that remodeling of the donor heart after transplantation is characterized by a specific increase in collagen I and fibronectin, whereas a change in other collagen subtypes was not observed.