In a prospective study of the results of 5582 consecutive two-dimensional echocardiographic examinations, hypertrophy of a localized region of the basal ventricular septum was identified in 26 patients. Proven diagnoses were coronary disease in five patients, coronary plus valvular disease in three, valvular disease in seven, and miscellaneous in four. Localized septal hypertrophy was the only cardiac diagnosis in seven patients. The ratio of the thickness of the hypertrophied area to that of the adjacent septum was greater than or equal to 1.7 (mean 1.93 +/- 0.19) in all patients. The ration of the length of the hypertrophied portion (mean 0.34 +/- 06) to the length (apex to base) of the septum was less than 0.39 in all but one patient. Although the mitral valve tended to be more anterior than expected in 20, other features of hypertrophic cardiomyopathy were generally lacking. Of four patients undergoing left ventricular angiography, the bulge was identified in only one in whom cranial-caudal angulation was added to the 60-degree left anterior oblique view. An autopsy was performed in one patient; the hypertrophy was identified, although results of microscopic examination showed no fiber disarray. These data suggest that, in most instances, localized septal hypertrophy is an incidental echocardiographic finding. The diagnosis of hypertrophic cardiomyopathy should generally not be made on the basis of this feature alone.