Stress echocardiography (stress echo) by means of isometric handgrip has been proven to be useful for detection of latent cardiac dysfunction in patients with mitral valve prolapse (MVP). In MVP with symptoms (symptomatic MVP), handgrip (HG) stress usually induced an abnormal response, i.e. a decrease in the ejection fraction (EF) in accordance with other echo indices. If an effective treatment with coenzyme Q10 (CoQ) is performed, the response becomes normal (increase in EF) and symptoms disappear. Four hundred consecutive symptomatic MVP were divided into 6 groups according to the dose of CoQ, i.e., 0.6-0.9, 1.0-1.4, 1.5-1.9, 2.0-2.4, 2.5-2.9 and 3.0-3.4 mg/kg/day and followed up with repeated HG. There was a strong relationship between the dose and the time needed for normalization. In the 3.0-to-3.4 mg group, the majority of patients acquired a normal response within 1 week. When a single blind test between CoQ (N = 8) and ATP (adenosine triphosphate, N = 8) groups was conducted, the number of patients normalized within 8 weeks was 7 in the former and 0 in the latter. After reduction of the dose, 41 patients had relapses (re-abnormalizations) within 15 weeks (mean = 6.6). Continuous normalization for 4 months or longer after termination of CoQ occurred 7 to 43 months (mean = 18.5) after onset of symptoms, probably reflecting the self-limited natural course. Some patients (5.8% of patients followed up) showed polycyclic long courses like those of congestive cardiomyopathy and needed long-term CoQ treatment. CoQ was definitely effective for symptomatic MVP and improved stress-induced cardiac dysfunction if the appropriate dose was given. No side-effect was seen.