We examined the relationship between interstitial cell infiltration and myocardial fibrosis in patients with clinically diagnosed dilated cardiomyopathy (DCM). Forty-two cases of DCM were divided into two groups, according to the mean number of the interstitial round cells per 10.2 x 10(4) square microns (Nic): the inflammatory group (Nic greater than or equal to 5) and noninflammatory group (Nic less than 5). The 12 cases in the inflammatory group were clinically similar to the 30 cases in the non-inflammatory group, but the inflammatory group exhibited a significantly (P less than 0.001) larger area of myocardial fibrosis (34.8% +/- 12.8% vs 17.5% +/- 8.2%), a significantly (P less than 0.01) higher frequency of diffuse perimyocytic-type fibrosis (83% vs 23%), fewer myocardial cells in the left ventricular wall (170 +/- 70 fibers vs 216 +/- 81 fibers), and significantly (P less than 0.01) greater hypertrophy of the myocytes (18.3 +/- 3.4 vs 15.3 +/- 2.7 microns). In addition, cases exhibiting marked fibrosis (fibrosis area greater than or equal to 25% of the myocardium) had a significantly higher Nic score (8.3 +/- 6.8) compared to cases with the less fibrotic type of DCM (4.0 +/- 5.7). We speculate that persistent or preceding inflammatory cell infiltration induces the myocardial fibrosis, especially the diffuse perimyocytic type, in the fibrosis-predominant type of DCM. Therefore, most of these cases may be a sequela of myocarditis, and more correctly termed post-myocarditic cardiomegaly.