The extracellular matrix between cardiocytes has been suggested to play an important role in maintaining the structure and function of the heart. The purpose of this study was to elucidate the morphological changes in the collagen of the extracellular matrix (ECM) in the hearts of pigs with hypertrophic cardiomyopathy. Sixty pigs diagnosed with hypertrophic cardiomyopathy from 605 purebred Landrace pigs ages 6 to 9 months were used in this study. Morphologically, these pigs with hypertrophic cardiomyopathy had increased heart weight and heart-to-body weight ratio, thickening of the left ventricular (LV) and right ventricular (RV) free walls and septum, disorientation of cardiocytes, myocardial fibrosis, and intramural coronary arteriosclerosis. Similar observations have been described in our preliminary report (Cardiovasc Pathol 3:261, 1994). In the present study, we have modified the silver impregnation technique to stain paraffin-embedded sections to demonstrate three types of ECM. There were endomysial struts, perimysial weaves, and epimysial coils in the myocardium. The light microscopic findings of the struts, weaves, and coils were also confirmed by scanning electromicroscopic examination. The numbers of these fine structures were increased significantly in the pigs with hypertrophic cardiomyopathy. In addition, the amounts of collagen in the LVs, RVs, and septum (Sep) in pigs with hypertrophic cardiomyopathy (LV = 19.37+/-0.79, RV = 23.72+/-0.72, Sep = 20.38+/-0.94 microg/mg, n = 60) were significantly higher (p < 0.01) than that in similar areas of normal pigs (LV = 14.56+/-1.11, RV = 18.90+/-1.02, Sep = 14.99+/-1.33 microg/mg, n = 30, respectively). Our findings of an overall increase of collagen content suggested that the accumulation of collagen matrix might be another factor responsible for the diastolic dysfunction of hypertrophic cardiomyopathy. These results might also infer that the increased collagen matrix could contribute to the stiffness of the cardiac chambers, thereby markedly affecting systolic and diastolic function of the heart. These observations provide further support that the pig may be an animal model for human cardiovascular disease.