BACKGROUND Necropsy studies in domestic cats have suggested the occurrence of a primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans. We used two-dimensional echocardiography to define morphological and functional features of HCM during life in 46 domestic cats evaluated in a subspecialty veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years). RESULTS During the follow-up period of as long as 49 months, 18 cats died (or were euthanatized) due to congestive heart failure, peripheral embolization, or both, and 3 other cats experienced out-of-hospital sudden, unexpected death. Echocardiography showed a small left ventricular cavity, associated with a variety of patterns of hypertrophy. Wall thickening was most often diffuse (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15 (33%), including 12 with thickening confined to anterior septum; wall thickening was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats (65%), marked mitral valve systolic anterior motion produced dynamic obstruction to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg). Compared with survivors, cats with HCM that died with heart failure had greater left ventricular thickness (8.1 +/- 1.5 versus 7.3 +/- 0.9 mm; P < .05) and larger left atria (20.1 +/- 4.6 versus 16.8 +/- 3.4 mm; P = .01) and more often had the nonobstructive form (89% versus 48%; P < .01). CONCLUSIONS A spontaneously occurring disease of domestic cats was identified by echocardiography and was similar in its phenotypic expression to HCM in humans; it was characterized by unexplained left ventricular hypertrophy in a variety of patterns with or without evidence of outflow obstruction. Unfavorable prognosis was associated with greater magnitude of hypertrophy and absence of outflow obstruction. Feline HCM may prove to be a valuable animal model of the human disease.