Endomyocardial biopsies from 174 patients with dilated cardiomyopathy (DC) were examined. Eight patients with histologically proven myocarditis were excluded from the study. A peculiar pattern of oversized and bizarre nuclei was observed in only some of the remaining patients. Two groups were identified: those with and without this feature (groups A and B, respectively). Myocyte width, nuclear diameter and nuclear/sarcoplasmic ratio were significantly higher in group A. The mean respective values were 36 +/- 5 mu, 14 +/- 3 mu and 0.41 +/- 0.08 for group A versus 20 +/- 8 mu, 7 +/- 2 mu and 0.37 +/- 0.08 for group B. Interstitial fibrosis was similarly present in groups A and B. Endocardial thickness was significantly increased in all patients, with group A showing the highest mean value. The morphologic features showed no correlation with the clinical condition of the patients at time of presentation. HLA typing was performed in 50 consecutive patients, 38 from group A and 12 from group B. DR4 and DR5 antigens were significantly more frequent in DC patients than in a normal population control (400 blood donors), while DR3 was less frequent. Group A was more strongly associated with the DR5 antigen than group B (55.3 vs 25.0%, respectively). It was less strongly associated with the DR4 antigen compared with group B (21.5 vs 41.7%, respectively). No difference was observed between the 2 groups concerning negative association with the DR3 antigen. Endomyocardial biopsies from DC patients reveal marked morphologic changes from patient to patient.(ABSTRACT TRUNCATED AT 250 WORDS)