Hypertrophic cardiomyopathy is associated with increased risk of arrhythmias and heart failure, and sudden cardiac death especially in younger people (McKenna et al. 2002). The hypertrophy is often asymmetric involving the septum and, in a proportion of patients there is left ventricular outflow obstruction. The histological hallmark is myocyte disarray and fibrosis. The cellular basis of the functional abnormalities is unclear and there is no extensive description of the electromechanical properties of human myocardium from such patients. Myocardial strips (≤1 mm diameter) were prepared from surgically excised, septal myocardium from 14 symptomatic patients with HOCM, and normal systolic function at rest. Samples were also snap-frozen in liquid N₂ for estimation by Western blotting of connexin43 (Cx43) protein (Peters et al. 1997). Electromechanical properties, including action potential morphology and conduction, isometric twitch characteristics and impedance properties were measured as described previously (Cooklin et al. 1997; Botchway et al. 2003). Data are mean±SD and compared where possible to a previous study (McIntyre & Fry, 1997) that used samples from patients with mitral stenosis (MS) and normal ventricular function. Differences between groups were tested with Student’s t test and the null hypothesis rejected at p<0.05. All samples had a negative force-frequency function; the tension ratio at 1.6 and 0.8 Hz stimulation was 0.84±0.09 and significantly less than the MS group (1.30±0.22). Time to peak tension generation was not significantly different in the two groups (262±31, 260±27 ms; HOCM vs MS), but time to relaxation was significantly longer in the HOCM group (402±43 vs 307±20 ms). Isoprenaline increased significantly tension generated at 1 Hz by 243±53% at 3 µM, with an EC₅₀ of 0.64±0.22 µM (n=5). Action potential duration (95% repolarisation) at 1Hz stimulation was significantly longer in the HOCM group (455±84 vs 342±11 ms), and often displayed early after-depolarisations at lower stimulation frequencies. Conduction velocity was also significantly less in HOCM samples (51.3±4.6 [n=6] vs 59.9±6.1 cm s^-1 (n=9)). A negative association (r=0.88, n=7) was observed between the amount of Cx43 protein (normalised to f-actin) and the intracellular resisitvity measured by impedance network analysis. We show that with myocardium from patients HOCM, action potential and twitch durations are both prolonged and that action potential conduction is also impaired. We propose that slowed conduction is due to reduced Cx43, and hence increased intracellular resistivity. These observations may explain why patients with HOCM tolerate tachycardia poorly and are prone to malignant arrhythmias.