To determine whether immunohistochemical analysis of cardiac biopsies from patients presenting clinically as dilated cardiomyopathy (DCM) show a chronic inflammatory process. Comparative case control study. Tertiary referral centre. Biopsies from 170 patients with DCM and 85 control patients with other cardiac diseases. Nine patients had sufficient interstitial inflammatory cells to be called borderline myocarditis on conventional histology, leaving 161 patients with DCM. In 78 patients with DCM (48%) there were T lymphocytes in the myocardium. In 48 (62%) of these 78 T lymphocyte densities were in the range 2-14 per high power field (HPF), equivalent to 7-50 per mm2 of tissue. In 43 (89%) interstitial and endothelial immune activation was demonstrated by MHC expression. In 30 patients with T cell counts in the range 1.5-2.0 per HPF, 80% also showed endothelial activation. Lymphocyte density correlated with increased expression of MHC class I and II antigens and the adhesion molecules ICAM, VCAM, ELAM, LFA-3, and GMP140. In all control biopsies the T lymphocyte density was less than 1.0 per HPF (less than 2-5 per mm2 of tissue). Nearly half the patients with DCM had increased T lymphocyte density and immune activation of endothelial and interstitial cells in their cardiac biopsies. A chronic autoimmune process is still active within the myocardium in a significant percentage of patients with DCM. Immunohistochemical analysis of cardiac biopsies will enhance the sensitivity of cardiac biopsy and is essential for the diagnosis of myocarditis.