Single photon emission computed tomography (SPECT) using I-123 metaiodobenzylguanidine (MIBG) was evaluated for the detection of doxorubicin (DXR) cardiomyopathy in seven patients with malignant lymphoma receiving DXR doses ranging from 70 to 530 mg (DXR group), and 20 normal subjects without hypertension, diabetes mellitus or electrocardiographic abnormalities (control group). The ratio of the heart to mediastinal counts (H/M) and the washout rate (WR) in MIBG SPECT images were compared between the two groups. Correlation of total doses of DXR with H/M and the relationship of H/M to WR were investigated. The H/M of the DXR group was lower than that of the control group (3.00 +/- 0.97 vs 4.90 +/- 1.08, p < 0.001). The WR of the DXR group was higher than that of the control group (30.9 +/- 10.5% vs 16.5 +/- 9.1%, p < 0.001). Total DXR doses were inversely correlated with H/M (r = -0.86), H/M correlated inversely with the WR (r = -0.83) only in the DXR group. Pathological findings of one patient, who died of DXR cardiomyopathy, showed atrophic and fibrotic nerve fibers in the apical inferior segment of the left ventricle where MIBG uptake was reduced markedly. DXR cardiomyopathy can be detected with MIBG SPECT as cardiac sympathetic nervous dysinnervation. The pathological findings correspond to the MIBG SPECT findings.