The development of segmental or generalized left ventricular hypokinesia is an unusual occurrence in patients with hypertrophic cardiomyopathy. To determine the incidence and possible pathophysiologic mechanisms responsible for this process, the serial clinical and laboratory data of 62 patients with the diagnosis of hypertrophic cardiomyopathy were analyzed. During a mean follow-up period of 8 years (range 2 to 21), 5 patients (Group A) developed left ventricular hypokinesia, whereas the remaining 57 patients (Group B) continued to exhibit the clinical and laboratory findings of hypertrophic cardiomyopathy. Three patients developed a dilated left ventricle with generalized hypokinesia; two other patients had segmental left ventricular wall motion abnormalities. None of these five patients who developed left ventricular hypokinesia had fixed coronary artery disease. The mean age, sex, mean duration of follow-up, presence of coronary myocardial bridges and angina pectoris, and an interventricular gradient were all similar in Groups A and B. Midventricular obliteration was seen in 4 (80%) of the 5 patients in Group A and in 4 (7%) of the 57 patients in Group B (p less than 0.001). Findings from this study reveal that segmental or generalized left ventricular hypokinesia can develop in patients with hypertrophic cardiomyopathy in the absence of fixed coronary artery disease. Such hypokinesia can occur after an acute myocardial infarction or it can develop gradually without clinical or electrocardiographic evidence of infarction. Patients with the mid-ventricular obliteration variant of hypertrophic cardiomyopathy are at a higher risk of developing segmental or diffuse left ventricular hypokinesia.