Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease less than or equal to 5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 +/- 15 vs 75 +/- 11%, respectively, p less than 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 +/- 7 vs 21 +/- 6 mm, p less than 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p less than 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p less than 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p less than 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.